483 research outputs found
Physiological responses to pedaling on a water stationary bike at different immersion heights
Only a few studies[1-4] have investigated oxygen consumption (VâO2) and heart rate (HR) responses to pedaling on a stationary bike in water (WSB), while literature is still lacking on the effects elicited by variations in immersion depth. 14 subjects (8 M, 6 F, age 30±6y, weight 67±14kg, BMI 22.8±2.3kg/m2, fat mass 21,4±3%) performed 2 testing sessions and 2 exercise sessions: i) dry-land incremental exercise test (cycle-ergometer) to age-predicted maximum HR (HR); ii) underwater (hip-height) incremental exercise test (on a WSB) to exhaustion; iii/iv) two 2-stage (18-minutes each) underwater pedaling exercises on a WSB (Aqquatix S.r.l., Italy) at 2 different immersion heights (armpit/hip). Breath-by-breath VâO2 and beat-by-beat HR were recorded continuously throughout dry-land sessions. The intensities of the exercise sessions were 45%-55% (stage#1) and 70%-80% (stage#2) of the underwater VâO2 peak (a metronome was set at the VâO2 peak pedaling rate). A repeated-measures (2 exercise intensities) 2-way (armpit/hip heights) ANOVA was performed on each variable and the Bonferroni test was used for post-hoc comparisons. Compared to the hip-height condition, pedaling immersed at the armpit level elicited significantly lower VâO2 and HR (significant solely at high-intensity for HR) responses, either exercising at high (25.5±4.6 vs. 29.1±4.8 mLâkg-1âmin-1; 127±14 vs. 140±19 beatsâmin-1) or low (17.9±3.6 vs. 20.1±3.6 mLâkg-1âmin-1; 105±16 vs. 110±15 beatsâmin-1) intensity. While peak VâO2 didnât differ significantly between dry-land and underwater tests (36.2±5.4 vs. 38.8±5.8 mLâkg-1âmin-1), mean HRs at both intensities and both water heights were significantly lower when expressed as percentage of the HR resulting from the underwater test to exhaustion, rather than applying the 220-age prediction equation.Universidad de MĂĄlaga. Campus de Excelencia Internacional AndalucĂa Tech
JCV-specific T-cells producing IFN-gamma are differently associated with PmL occurrence in HIV patients and liver transplant recipients
Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LT
Autophagy modulation in lymphocytes from COVID-19 patients. new therapeutic target in SARS-COV-2 infection
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the novel coronavirus, causing coronavirus disease 2019 (COVID-19). During virus infection, several pro-inflammatory cytokines are produced, leading to the âcytokine storm.â Among these, interleukin (IL)-6, tumor necrosis factorâα (TNFâα), and IL-1ÎČ seem to have a central role in the progression and exacerbation of the disease, leading to the recruitment of immune cells to infection sites. Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. The involvement of IL-6, TNFâα, and IL-1ÎČ in autophagy modulation has recently been demonstrated. Moreover, preliminary studies showed that SARS-CoV-2 could infect lymphocytes, playing a role in the modulation of autophagy. Several anti-rheumatic drugs, now proposed for the treatment of COVID-19, could modulate autophagy in lymphocytes, highlighting the therapeutic potential of targeting autophagy in SARS-CoV-2 infection
FRI0376â EFFECT OF CARBAMYLATED LOW-DENSITY LIPOPROTEINS ON BONE CELLS HOMEOSTASIS
Background:Carbamylation is a post-translational modification occurring under several conditions such as uremia, smoking and chronic inflammation as in rheumatoid arthritis (RA). Low-density lipoproteins (LDL) represent a target of carbamylation. Carbamylated-LDL (cLDL) have an increased inflammatory and atherogenic potential. Growing evidence supports an influence of modified lipids on bone cells homeostasis. However, the role of cLDL on bone cells physiology is still unknown.Objectives:Considering the rate of carbamylation and the role of anti-carbamylated proteins antibodies as markers of erosive disease in RA, the purpose of this study is to investigate the effect of cLDL on bone homeostasis.Methods:In-vitrocarbamylation of LDL was performed as previously described by Ok et al. (Kidney Int. 2005). Briefly, native LDL (nLDL) were treated with potassium cyanate (KOCN) for 4 hours, followed by excessive dialysis for 36 hours to remove KOCN. Both osteoclasts (OCs) and osteoblasts (OBLs) were treated at baseline with 20 ÎŒg/ml, 100 ÎŒg/ml and 200 ÎŒg/ml of cLDL or nLDL. To induce osteoclast differentiation, CD14+ monocytes were isolated from peripheral blood of healthy donors by magnetic microbeads separation and then cultured on a 96-wells plate in DMEM media supplemented with RANKL and M-CSF. After 10 days cells were fixed, stained for tartrate-resistant acid phosphatase (TRAP), a marker of OC differentiation, and counted. OBLs were isolated from bone specimens of 3 patients who had undergone to knee or hip arthroplasty for osteoarthritis and treated for 5 days with different concentrations of cLDL and nLDL. OBLs were fixed and stained for alkaline phosphatase positive activity (ALP), a marker of osteogenic differentiation. Total RNA was extracted from cell lysates. Copies of single-stranded complementary DNA (cDNA) were synthesized and analyzed by real-time PCR to evaluate RANKL and Osteoprotegerin (OPG) mRNA expression levels.Results:In OCLs culture, cLDL significantly decreased the number of OC compared to untreated cells (200 ÎŒg/ml p=0,0015) and nLDL treated cells (200 ÎŒg/ml p= 0,011; 20 ÎŒg/ml p= 0,0014) (Fig 1). Moreover, treatment with cLDL induced an increase of not terminally differentiated OCs, reduced dimensions of OCs, less intense TRAP staining and vacuolization (Fig 2). In OBLs culture, cLDL (20, 100 ÎŒg/ml) significantly reduced the ALP activity of OBLs compared with untreated cells (p<0.05) (Fig 3). nLDL did not affect the ALP expression. Treatment with cLDL stimulated RANKL mRNA expression in osteoblasts increasing the RANKL/OPG ratio (Fig 4).Fig 1.Fig 2.Fig 3.Fig 4.Conclusion:cLDL induce a significant depression of OC and OBL differentiation. Moreover, cLDL increase RANKL expression in OBL, unbalancing bone tissue turnover towards bone resorption. Accordingly, cLDL could be implicated in the bone loss characterizing several conditions associated to an increased carbamylation, such as RADisclosure of Interests:Bruno Lucchino: None declared, Martina Leopizzi: None declared, Tania Colasanti: None declared, Valeria Di Maio: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Manuela Di Franco: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lill
Emergenza sismica nel Frusinate (Ottobre 2009 â Gennaio 2010): lâintervento della Rete Sismica Mobile stand-alone e lâanalisi dati
Tra il 30 settembre ed il 22 ottobre del 2009 una piccola area della provincia di Frosinone, presso la localitaÌ di Campoli Appennino, non lontana dalla cittaÌ di Sora e dal confine con lâAbruzzo, eÌ stata interessata da uno sciame sismico la cui fase piuÌ intensa eÌ stata raggiunta nella notte tra il 7 e lâ8 di ottobre con due scosse di magnitudo locale (ML) 3.6 e 3.4. Nei primi 23 giorni della sequenza (30 settembre â 22 ottobre) sono state registrate ben 1075 scosse, tutte con magnitudo non superiore a 3.6. In precedenza, nei mesi di maggio e giugno del 2009, si era attivata una piccola area posta ad una quindicina di chilometri a NW di Campoli Appennino, esattamente nella zona montuosa che separa la Val Roveto dalla Vallelonga in territorio abruzzese. Questo piccolo sciame eÌ stato caratterizzato da 64 eventi con ML non superiore a 2.7.
Diverse sono state le ragioni che hanno indotto il team scientifico alla guida della Rete Sismica Mobile della sede di Roma [Re.Mo., Moretti et al., 2010a] a disporre nei primi giorni del mese di ottobre un intervento di emergenza nellâarea che include i comuni di Sora, Atina, San Donato in Val Comino e Pescasseroli tra le provincie di Frosinone e de LâAquila: 1) la relativa vicinanza delle due zone epicentrali sopra descritte alla regione dellâAquilano colpita solo pochi mesi prima dal forte evento sismico del 6 aprile 2009 (ML 5.8, MW 6.31) [Chiarabba et al., 2009; Margheriti et al., 2010], 2) lâemotivitaÌ della popolazione originatasi a seguito del forte trauma vissuto e 3) non ultimo la psicosi collettiva notevolmente alimentata dai media locali e nazionali. In tutto, sono state installate 4 stazioni sismiche temporanee ad integrazione delle permanenti giaÌ presenti in area epicentrale al fine di migliorarne il monitoraggio.
In questo lavoro viene presentato lâintervento della Re.Mo. riportando le motivazioni che lo hanno guidato e la tempistica delle operazioni svolte. Inoltre, verraÌ fornita una breve descrizione delle caratteristiche geologico-strutturali e sismotettoniche dellâarea e saranno mostrate alcune analisi eseguite sui dati acquisiti in campagna
La Rete Sismica Mobile del Centro Nazionale Terremoti
Il monitoraggio sismico e vulcanico del territorio nazionale rappresenta uno dei principali compiti
istituzionali dellâIstituto Nazionale di Geofisica e Vulcanologia (INGV).
LâINGV svolge tale importante funzione attraverso la gestione e la manutenzione di reti sismiche di
diversa tipologia e a differente scala che consentono di monitorare il territorio nazionale in tempo reale. Tre
sale di sorveglianza, una sismica presso la sede centrale di Roma e due vulcaniche presso la Sezione di
Catania e lâOsservatorio Vesuviano di Napoli, con personale qualificato in turno H24, consentono di
elaborare e comunicare tempestivamente al Dipartimento della Protezione Civile Nazionale (DPC) e alle sue
strutture regionali eventuali stati di allarme e il livello dellâemergenza.
Il Centro Nazionale Terremoti (CNT) Ăš la sezione dellâINGV preposta al monitoraggio sismico del
territorio italiano ed interviene in questo importante servizio attraverso la gestione e la manutenzione della
Rete Sismica Nazionale (RSN) in collaborazione con le altre sedi dellâINGV dislocate sul territorio e con gli
uffici tecnici locali. Competenza del CNT Ăš anche la rete sismica euro-mediterranea (MedNet): una rete di
stazioni sismiche a larga banda dislocate nei Paesi che circondano il Mediterraneo in condivisione con molti
istituti geofisici. Negli ultimi anni tali reti sono cresciute sia come numero di stazioni che come tecnologia,
consentendo di controllare in maniera estesa lo spettro di frequenze emesse dalla sorgente sismica e la
ciclicitĂ delle strutture sismogenetiche.
In alcune aree del territorio nazionale lâalta densitĂ di tali reti sismiche rende possibile una soglia di
detezione degli eventi molto bassa e localizzazioni di elevata precisione che permettono di associare la
micro-sismicitĂ alle strutture sismo-genetiche. Tuttavia questo non Ăš tecnicamente ed economicamente
possibile in maniera omogenea su tutto il territorio nazionale. Per tale motivo si fa spesso ricorso allâuso di
reti temporanee in esperimenti mirati allo studio di aree a peculiare rischio sismico e vulcanico o, in caso di
forti terremoti, per aumentare la densitĂ della rete giĂ presente e migliorare il monitoraggio in real-time in
modo tale da analizzare con maggior dettaglio lâevoluzione della sequenza.
UnitĂ specializzate nella gestione di reti sismologiche temporanee sono presenti in diverse sedi
dellâINGV. Esse lavorano in completa autonomia sul territorio di competenza ma sono in grado di realizzare
un buon livello di sinergia lĂ dove esperimenti ed emergenze sismiche richiedano una stretta collaborazione.
La struttura piĂč grande, sia come numero di strumenti a disposizione (piĂč di 200 tra digitalizzatori e sensori)
che come personale impegnato, Ăš la Rete Sismica Mobile (RSM) del CNT che Ăš organizzata in modo da
rendere possibile lâimpiego della strumentazione in piĂč esperimenti mantenendo una quota di strumenti
riservata per gli interventi di emergenza.
In questo rapporto tecnico presentiamo la struttura organizzativa ed operativa della RSM del CNT, la
strumentazione in uso presso di essa e le diverse configurazioni possibili per le stazioni sismometriche
temporanee con lâobiettivo di fornire un manuale dâuso ai ricercatori, tecnologi e tecnici che si interfacciano
con la RSM, sia durante lâattivitĂ scientifica ordinaria (esperimenti di sismica passiva e attiva) che
straordinaria (emergenze sismiche)
Anti-D4GDI antibodies activate platelets in vitro. a possible link with thrombocytopenia in primary antiphospholipid syndrome
Background: Thrombocytopenia is a manifestation associated with primary antiphospholipid syndrome (PAPS), and many studies have stressed the leading role played by platelets in the pathogenesis of antiphospholipid syndrome (APS). Platelets are highly specialized cells, and their activation involves a series of rapid rearrangements of the actin cytoskeleton. Recently, we described the presence of autoantibodies against D4GDI (Rho GDP dissociation inhibitor beta, ARHGDIB) in the serum of a large subset of SLE patients, and we observed that anti-D4GDI antibodies activated the cytoskeleton remodeling of lymphocytes by inhibiting D4GDI and allowing the upregulation of Rho GTPases, such as Rac1. Proteomic and transcriptomic studies indicate that D4GDI is very abundant in platelets, and small GTPases of the RHO family are critical regulators of actin dynamics in platelets. Methods: We enrolled 38 PAPS patients, 15 patients carrying only antiphospholipid antibodies without clinical criteria of APS (aPL carriers) and 20 normal healthy subjects. Sera were stored at - 20 °C to perform an ELISA test to evaluate the presence of anti-D4GDI antibodies. Then, we purified autoantibodies anti-D4GDI from patient sera. These antibodies were used to conduct in vitro studies on platelet activation. Results: We identified anti-D4GDI antibodies in sera from 18/38 (47%) patients with PAPS, in sera from 2/15(13%) aPL carriers, but in no sera from normal healthy subjects. Our in vitro results showed a significant 30% increase in the activation of integrin αIIbÎČ3 upon stimulation of platelets from healthy donors preincubated with the antibody anti-D4GDI purified from the serum of APS patients. Conclusions: In conclusion, we show here that antibodies anti-D4GDI are present in the sera of PAPS patients and can prime platelet activation, explaining, at least in part, the pro-thrombotic state and the thrombocytopenia of PAPS patients. These findings may lead to improved diagnosis and treatment of APS
CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögrenâs syndrome patients and correlates with focus score and disease activity
Background: Primary Sjögrenâs syndrome (pSS) is a common chronic autoimmune disease characterized by
lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we
aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS.
Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a
nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS
disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed
for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral
blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked
immunosorbent assay.
Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary
glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte
autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy
enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate
and adaptive immune responses in pSS.
Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis.
Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and
provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS
La campagna sismica del progetto âAlto Adriaticoâ. Rapporto delle attivitĂ 2010-2011
Istituto Nazionale di Geofisica e VulcanologiaPublished1-401.1. TTC - Monitoraggio sismico del territorio nazionaleN/A or not JCRope
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