1,721,001 research outputs found
Acromegalia e Ancona: un fil rouge lungo trecento anni, da Amato Lusitano ad Augusto Tamburini
Full text linkAncona è diventata sede universitaria in tempi recenti, sol-
tanto un cinquantennio fa, ma le sue strutture sanitarie, il
manicomio e l’ospedale, avevano un rilievo regionale o in-
terregionale già nella prima metà del Novecento [29]. Me-
dici originari di Ancona, come Augusto Tamburini, sebbene
abbiano costruito altrove la loro carriera, hanno comunque
contribuito allo sviluppo della città e delle sue istituzioni,
e la biblioteca dell’ex-manicomio a lui intitolata costituisce
uno strumento prezioso per lo studio della psichiatria, della
neurologia e, più in generale, della medicina tra fine Otto-
cento e primo Novecento, compresa l’acromegalia. Ancona,
inoltre, da sempre città di mare, centro di commerci e scam-
bi con l’Oriente e il Mediterraneo, ha ospitato seppure per breve tempo, a metà del Cinquecento, uno straordinario me-
dico itinerante, l’ebreo portoghese Amato Lusitano, la cui
opera conserva memorie altrimenti perdute della città e del
suo territorio, tra cui la storia del gigante di Senigallia
Supplemental Material, Appendix_A_(1) - Personality (at Intrapsychic and Interpersonal Level) Associated With Quality of Life in Patients With Cancer (Lung and Colon)
No full textSupplemental Material, Appendix_A_(1) for Personality (at Intrapsychic and Interpersonal Level) Associated With Quality of Life in Patients With Cancer (Lung and Colon) by Maria Velia Giulietti, Anna Vespa, Marica Ottaviani, Rossana Berardi, Giancarlo Balercia, Giorgio Arnaldi, Pisana Gattafoni, Paolo Fabbietti, Mirko Di Rosa and Roberta Spatuzzi in Cancer Control</p
UNRAVELING THE POTENTIAL ROLE OF A SMALLEXTRACELLULAR VESICLE LYOPHILIZED ENRICHEDIN IMMUNE AND INFLAMMATORY REGULATOR FACTORS AS IMMUNORESPONSE MODULATOR INPATIENTS SUFFERING FROM AUTOIMMUNE THYROID DISEASES
No full textIn Autoimmune Thyroid Diseases (AITDs), a loss of toler-ance to thyroid antigens and lymphocyte infiltration into the thyroid gland occurs. An imbalance in T helper type (Th)-17 and regulatory T lymphocytes (Tregs) contributes to perpetuate the inflammatory state leading to thyroid dysfunction and disruption. Although the replacement of hormone production represents the main aim in therapeu-tic treatment, a deeper understanding of the mechanism regulating the immune response improving inflammation could represent an important outcome in AITDs. In our previous study, we described an in vitro coculture model elucidating the ability of Th-1 cytokines licensed fibrob-last-like Limbal mesenchymal Stem Cells (f-LSCs) to reg-ulate T-cell activity in patients suffering from AITDs by an altered cytokine profile via downregulation of human het-erogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) isoforms, which were found overexpressed in peripheral blood mononuclear cells (PBMCs) collected from patient suffering from AITDs1-2. Unfortunately, the clinical application of human mesenchymal stem cells (MSCs) is hampered by legal and ethical issues. Noteworthy, MSC immunomodulator capability depends also by soluble products, which could be conveyed by Small Extra Vesicles (sEVs), nanoscale cell-derived struc-ture of 200 nm less in size. Data here reported demon-strate for the first time that a reconstituted lyophilized of sEVs (sEVLyo) derived TH-1 cytokines licensed f-LSCs retains the anti-inflammatory and immunomodulation capabilities in activated PBMCs from AITD patients, simi-lar to f-LSCs. As the lack of comparative studies assessing the efficacy of different EV isolation techniques hinders clinical use of sEVs, we firstly compared two different sEV isolation methods tangential flow filtration (TFF) and pre-cipitation. Once obtained, sEVs were lyophilized and char-acterized for size distribution, protein content, and purity by detection of CD63, CD9, CD81, specific sEVs surface markers. To explore the sEV anti-inflammatory and immune modulation properties, activated PBMCs from AITD patients were exposed to different concentrations of sEVLyo and several functional biological assays were per-formed. We demonstrate that sEVs improve the autoreac-tive response in PBMC from AITD patients, inhibiting CD8+Tcell proliferation, CD69+ and CD25+ expansion with-in CD4+Tcells. Among several anti-inflammatory and immunosuppressive markers modulated, i.e. IDO, PDL-1, MCP-1 and IL-4, hnRNP A2/B1 were found downregulated in activated PBMC under sEVLyo exposure. Finally, we pro-pose that TH-1 licensing enriched sEV in specific benefi-cial factors, including PD-L1, COX-2, TXN-1. Indeed, we confidently promote the lyophilization as a valid storage method to satisfyingly preserve functional sEVs, encour-age their emerging role as an alternative approach to stem cell therapy highlighting the possibility to modulate their protein content, once again suggesting hnRNP A2/B1 as potential target in AITDs
Ketogenic Diet in Steatotic Liver Disease: A Metabolic Approach to Hepatic Health
Full text linkMetabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver dysfunction worldwide, characterized by hepatic steatosis that may progress to nonalcoholic steatohepatitis and cirrhosis. Owing to its strong association with metabolic disorders, current management focuses on weight reduction via lifestyle modifications. Recently, the very-low-calorie ketogenic diet (VLCKD) has emerged as a promising intervention due to its potential for rapid weight loss and reduction in liver fat. This review aims to evaluate the clinical evidence regarding the impact of ketogenic diets on hepatic steatosis. We conducted an extensive MEDLINE literature search in databases including PubMed, Scopus, and Web of Science up to December 2024. Studies assessing the effects of ketogenic or low-carbohydrate high-fat diets on liver fat, evaluated by imaging, histology, or biochemical markers, were included. The analysis indicates that ketogenic diets significantly reduce hepatic fat content and improve metabolic parameters, including insulin sensitivity and liver enzyme levels. Evidence further suggests that substituting saturated fats with unsaturated fats or replacing carbohydrates with proteins may enhance these benefits. However, considerable variability exists among studies and long-term data remain limited. Although short-term outcomes are encouraging, potential adverse effects such as dyslipidaemia, gastrointestinal disturbances, and transient ‘keto flu’ symptoms require careful clinical monitoring. Future research should focus on elucidating underlying mechanisms, optimizing dietary composition, and assessing long-term safety to establish ketogenic diets as a robust strategy for managing MASLD
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency
Full text linkObjective: The primary outcome was the evaluation of the T-cell phenotype in autoimmune primary adrenal insufficiency (PAI). Secondary outcomes included the evaluation of the CD4+CD25+Foxp3+ Treg population and the gene expression levels of IL-6, IL-17A, cyclooxygenase (COX)-2, heat shock proteins (HSP)-70, indoleamine-2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1), inducible nitric oxide synthase (iNOS), and thioredoxin (TXN)-1.
Methods: We prospectively included 15 patients with PAI on conventional glucocorticoid (GC) replacement therapy, 15 switched to dual-release hydrocortisone (DR-HC), and 20 healthy controls. Serum inflammatory parameters and peripheral blood mononuclear cells (PBMCs) were evaluated at baseline and after 12 months of treatment.
Result: At baseline, significantly higher CD4+ and CD8+ (both p < 0.001) T-cell percentages, a lower CD4+/CD8+ ratio (p < 0.05), and higher CD25+ and CD4+/CD25+ T cells (both p < 0.001) were observed in PAI compared to controls. After 12 months of DR-HC treatment, we found significantly lower IL-6 (p = 0.019), IL-17A (p = 0.046), COX-2 (p < 0.001), HSP-70 (p = 0.006), and TXN-1 (p = 0.008) and higher PD-L1 (p < 0.001) and IDO (p < 0.001) mRNA values compared to baseline. After 12 months of DR-HC treatment, a significant increase in CD4+ T cells (p = 0.012), PD-L1 (p = 0.003), and IDO (p < 0.001) and a decrease in CD8+ T cells (p < 0.001), IL-6 (p = 0.003), IL-17A (p = 0.0014), COX-2 (p < 0.001), HSP-70 (p = 0.005), and TXN-1 (p = 0.0008), as well as a significantly higher conversion in the CD4+/CD8+ ratio (p = 0.033), were observed compared to conventional GCs.
Conclusions: The switch from conventional GCs to DR-HC treatment altered the T lymphocyte phenotype and CD4+/CD8+ ratio in a Treg-independent manner, inducing significant improvements in the immune and inflammatory profile in PAI
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Apparent mineralocorticoid excess type II
No full textThe syndrome of apparent mineralocorticoid excess (AME) is currently understood to reflect impaired peripheral metabolism of cortisol, which is then able to activate the non-selective mineralocorticoid (MC) receptor. The failure of glucocorticoid inactivation at the MC target tissue level in AME involves abnormal activity of 11 beta-hydroxysteroid dehydrogenase, with impaired conversion of cortisol to cortisone, and also of 5 beta-reductase. We have discovered a new form of AME (Type II) in four patients with the same clinical picture of hypertension, hypokalemia, and suppressed renin-angiotensin-aldosterone system, but in whom this conversion seems either to be normal (since cortisol to cortisone metabolite ratio is normal) or to be impaired in both directions, leaving the ratio unchanged. Both types are characterized by a profound decrease in cortisol turnover quotient and Ring A reduction constant. Short-term dexamethasone treatment is effective in correcting the MC-derived abnormalities, while in the long term the addition of other antihypertensive drugs may be required to control the severity of hypertension
CONVENTIONAL GLUCOCORTICOID REPLACEMENT THERAPY VS. DUAL-RELEASE HYDROCORTISONE: EFFECTS ON INFLAMMATION AND IMMUNE PROFILE IN PATIENTS WITH PRIMARY ADRENAL INSUFFICIENCY AND IMPLICATIONS OF THERAPY RESPONSE PREDICTORS
No full textPrimary adrenal insufficiency (PAI), whose autoimmune adrenalitis is the main cause, is characterised by an inadequate cortisol secretion, due to a destruction of adrenal gland and a consequent lack of glucocorticoid and mineralocorticoid production. Autoimmune conditions are caused by a loss of tolerance for self-antigens, with regulatory T lymphocytes failing in limiting auto-reactivity, and the increase of pro-inflammatory processes. Generally, corticosteroids exert anti-inflammatory and immunosuppressive actions by regulating the expression of inflammatory and immunomodulatory proteins and by modulating the lymphocyte pattern, including the regulatory T-cells (Tregs) induction. Conventional glucocorticoids - including cortisone acetate and hydrocortisone administered two or three times a day - are the mainstay of the treatment of patients with PAI, but in the most recent years the innovative dual-release hydrocortisone (DR-HC) - administered once daily - has been used as replacement therapy. DR-HC has shown favourable effects on cardiovascular risk factors, glucose metabolism and bone parameters compared to conventional steroids. Moreover, it has shown to improve the immune system cell profile expression, restoring a more physiological circadian glucocorticoid rhythm. According to this evidence, this study investigates whether conventional replacement steroid (CRS) or DR-HC elicit different response in terms of anti-inflammatory or immunomodulatory effects, by measurement of anthropometric, metabolic, serum inflammatory parameters and gene expression levels of IL-6, IL-17A, COX-2, HSP-70, IDO, PD-L1, hnRNPA2/B, iNOS and TXN-1. Additionally, a cytofluorimetric analysis was performed to evaluate a modulation in the activation status of T-cells, including CD4+CD25+Foxp3+Treg population. The study included 15 patients with PAI on conventional glucocorticoid therapy and 15 patients on DR-HC. The outcomes of the study were evaluated by isolation of peripheral blood mononuclear cells at baseline and after 12 months of treatment. 10 healthy patients (controls) were evaluated at the time of enrolment. In patients treated with CRS, a significant increase in c-reactive protein, erythrocyte sedimentation rate and fibrinogen were observed after 12 months of treatment compared to baseline. At 12 months, significantly lower waist circumference, glucose, c-reactive protein, erythrocyte sedimentation rate and neutrophile-to-lymphocyte ratio was observed in patients treated with DR-HC compared to those treated with conventional treatment. A significant decrease in the transcription of COX-2 and HSP-70 (along with IL-6) was observed together with a significant increase in mRNA expression of IDO and PD-L1 in patients treated with DR-HC after 12 months of observation. Compared to CRS, DR-HC treatment improves the inflammatory and immune patterns in patients with PAI modulating several proteins involved in inflammatory response in a Treg-independent manner. Moreover, we can suppose that the transcription levels of IL-6, COX-2, HSP-70, IDO and PD-L1 could be considered to predict and evaluate the response to steroidal therapies in PAI and their different efficacies, based on our findings on anthropometric, metabolic, and biochemical outcomes. However, further larger and controlled studies are needed to confirm our preliminary results and the relevance of this assumption
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