2,980 research outputs found
Prion expression is activated by Adenovirus 5 infection and affects the adenoviral cycle in human cells
The prion protein is a cell surface glycoprotein whose physiological role remains elusive, while its implication
in transmissible spongiform encephalopathies (TSEs) has been demonstrated. Multiple interactions between
the prion protein and viruses have been described: viruses can act as co-factors in TSEs and life cycles of
different viruses have been found to be controlled by prion modulation.
We present data showing that human Adenovirus 5 induces prion expression. Inactivated Adenovirus did
not alter prion transcription, while variants encoding for early products did, suggesting that the prion is
stimulated by an early adenoviral function. Down-regulation of the prion through RNA interference showed
that the prion controls adenovirus replication and expression.
These data suggest that the prion protein could play a role in the defense strategy mounted by the host
during viral infection, in a cell autonomous manner. These results have implications for the study of the prion
protein and of associated TSEs
Criminological Treatment of Abusing Partners
Criminological rehabilitative treatments of abusive partners have always been considered of key impor- tance from a preventive point of view. Criminological research, and our experience as criminologists, has proved that even the most abusive partners\u2014including uxoricides\u2014after their convictions repeat the same violent relationship pattern. That said, the Chair of Criminology (University of Milan) set up the first action and research program in Italy offering treatment for perpetrators of domestic violence, called S.A.Vi.D. (Stop Alla Violenza Domestica \u2013 an Italian acronym meaning: Stopping Domestic Violence) in 2010. Information about all the subjects treated will also be described and discussed: age, legal sta- tus motives, offender behavior prior to treatment, whether and how behavior changed after treatment
Vaccination with endosomal unknown epitopes produces therapeutic response in rheumatoid arthritis patients and modulates adjuvant arthritis of rats
BACKGROUND:
Our previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and freed the autoantigens which in turn stimulated the immunoregulatory rather than autoreactive T cell response in rheumatoid patients. Here, we hypothesize that disruption in vitro of peripheral blood mononuclear cells, by freeze/thawing or by lytic action of Rifamycin SV, would induce the release of endosomal pathogenic autoantigens from APCs present in the circulation, which could then be isolated from degrading enzymes by ultrafiltration.
METHODS:
The preparation of the ultrafiltrates are based on the rupture of PBMCs (5
7 10(6) cells/mL) by the addition of Rifamycin SV in culture (250 \u3bcg/mL), which causes the lysis of 90 % of the cells in 3 h, or by three cycles of freeze/thawing of the PBMC, from -80 \ub0C to room temperature. The lysate and the fragmented cells were then centrifuged and ultrafiltered by passage through a filtration device with a cut-off of 10 kDa. Also the synovial fluid was subjected to ultrafiltration.
RESULTS AND CONCLUSIONS:
At clinical monitoring of the 30th day, 22/58 (38 %) patients subcutaneously treated with the autologous ultrafiltrate prepared by the freeze/thawing of PBMCs reached an ACR20. Comparable results were obtained with the other two ultrafiltrates. Cell cultures The addition of ultrafiltrates to rheumatoid PBMCs cultures led to the upregulation of a marker for T-regulatory cells, and downregulation of a cell proliferation marker; changes that together have the meaning of a global immunomodulatory response and that only a specific antigen (ultrafiltrate UF-f/t) might induce in the rheumatoid patient, probably by activating pre-existing protective network. Experimental arthritis All the ultrafiltrates except that prepared by Rifamycin SV were able to modulate the adjuvant arthritis in rats. In particular, longlasting synovial fluid induced a significant reduction of the severity of subsequent arthritis (p < 0.01) while SF from recent RA effusion (5-10 days after a previous complete extraction) and knee osteoarthrosis were ineffective. It is reasonable to assume there are at least two unknown endosomal immunoactive epitopes; one developing its immunotherapeutic property in RA, and the other, related to the molecule of HSP60, reduces the severity of oncoming arthritis. Both epitopes are present in humans, have a molecular weight of 6410 kDa and do not appear to be bystander antigens. Please see Additional file 1 for the abstract in Italian
Mariticide in Milan between 1990 and 2017 : a criminological and medico-legal analysis
Most murder victims in a romantic relationship are women but sometimes they will kill their husbands or partners (mariticide). This paper focuses on these rarer cases using a sample taken from the autopsy reports of the Department of Legal Medicine of the University of Milan whose territory includes the municipality of Milan and part of the province of Milan and Monza \u2013 approximately four million inhabitants
Cardiovascular and Renal Effectiveness of GLP-1 Receptor Agonists vs. Other Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Studies
Cardiovascular outcome trials (CVOT) showed that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) is associated with significant cardiovascular benefits. However, CVOT are scarcely representative of everyday clinical practice, and real-world studies could provide clini-cians with more relatable evidence. Here, literature was thoroughly searched to retrieve real-world studies investigating the cardiovascular and renal outcomes of GLP-1RA vs. other glucose-lowering drugs and carry out relevant meta-analyses thereof. Most real-world studies were conducted in populations at low cardiovascular and renal risk. Of note, real-world studies investigating cardio-renal outcomes of GLP-1RA suggested that initiation of GLP-1RA was associated with a greater benefit on composite cardiovascular outcomes, MACE (major adverse cardiovascular events), all-cause mortality, myocardial infarction, stroke, cardiovascular death, peripheral artery disease, and heart failure compared to other glucose-lowering drugs with the exception of sodium-glucose transporter-2 inhibitors (SGLT-2i). Initiation of SGLT-2i and GLP-1RA yielded similar effects on composite cardiovascular outcomes, MACE, stroke, and myocardial infarction. Conversely, GLP-1RA were less effective on heart failure prevention compared to SGLT-2i. Finally, the few real-world studies addressing renal outcomes suggested a significant benefit of GLP-1RA on estimated glomerular filtration rate (eGFR) reduction and hard renal outcomes vs. active comparators except SGLT-2i. Further real-world evidence is needed to clarify the role of GLP-1RA in cardio-renal protection among available glucose-lowering drugs
Cabergoline as an adjuvant to standard heart failure treatment in peripartum cardiomyopathy: a case report and review of the literature
Introduction: Peripartum cardiomyopathy (PPCM) is a rare and idiopathic form of dilated cardiomyopathy presenting late in pregnancy or early postpartum. Since the 16-kDa fragment of prolactin has been identified as a key factor in the pathophysiology of PPCM, prolactin inhibitors have been used as an adjuvant to standard heart failure treatment. Although bromocriptine is the current first choice, promising results have been reported with cabergoline, albeit scant. Case Presentation: We presented the case of a 41-year-old woman who received a diagnosis of PPCM one week after delivery and was successfully treated with cabergoline, finally experiencing a complete recovery. Conclusion: The case adds to the scant evidence supporting the use of cabergoline in PPCM patients. We argue that the favorable pharmacokinetic and metabolic profiles of this drug should prompt its consideration as a valid alternative prolactin inhibitor in these critical patients
Novel patient-centered approach to facilitate same-day discharge in patients undergoing elective percutaneous coronary intervention
Background
Sameâday discharge (
SDD
) after elective percutaneous coronary intervention is safe, less costly, and preferred by patients, but it is usually performed in lowârisk patients, if at all. To increase the appropriate use of
SDD
in more complex patients, we implemented a âpatientâcenteredâ protocol based on risk of complications at BarnesâJewish Hospital.
Methods and Results
Our objectives were as follows: (1) to evaluate time trends in
SDD
; (2) to compare (a) mortality, bleeding, and acute kidney injury, (b) patient satisfaction, and (c) hospital costs by
SDD
versus no SDD (
NSDD
); and (3) to compare
SDD
eligibility by our patientâcentered approach versus Society for Cardiovascular Angiography and Interventions guidelines. Our patientâcentered approach was based on prospectively identifying personalized bleeding, mortality, and acute kidney injury risks, with a personalized safe contrast limit and mitigating those risks. We analyzed BarnesâJewish Hospital's National Cardiovascular Data Registry Cath
PCI
Registry data from July 1, 2009 to September 30, 2015 (N=1752).
SDD
increased rapidly from 0% to 77% (
P
<0.001), independent of radial access. Although
SDD
patients were comparable to
NSDD
patients,
SDD
was not associated with adverse outcomes (0% mortality, 0% bleeds, and 0.4% acute kidney injury). Patient satisfaction was high with
SDD
. Propensity scoreâadjusted costs were 7331 lower/
SDD
patient (
P
<0.001), saving an estimated 1.8Â million annually. Only 16 patients (6.95%) met the eligibility for
SDD
by Society for Cardiovascular Angiography and Interventions guidelines, implying our patientâcentered approach markedly increased
SDD
eligibility.
Conclusions
With a patientâcentered approach,
SDD
rapidly increased and was safe in 75% of patients undergoing elective percutaneous coronary intervention, despite patient complexity. Patient satisfaction was high, and hospital costs were lower. Patientâcentered decision making to facilitate
SDD
is an important opportunity to improve the value of percutaneous coronary intervention.
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SU(3) Mixing for Excited Mesons
The SU(3)-flavor symmetry breaking and the quark-antiquark annihilation
mechanism are taken into account for describing the singlet-octet mixing for
several nonets assigned by Particle Data Group(PDG). This task is approached
with the mass matrix formalism
Polyelectrolyte Multilayering on a Charged Planar Surface
The adsorption of highly \textit{oppositely} charged flexible
polyelectrolytes (PEs) on a charged planar substrate is investigated by means
of Monte Carlo (MC) simulations. We study in detail the equilibrium structure
of the first few PE layers. The influence of the chain length and of a (extra)
non-electrostatic short range attraction between the polycations and the
negatively charged substrate is considered. We show that the stability as well
as the microstructure of the PE layers are especially sensitive to the strength
of this latter interaction. Qualitative agreement is reached with some recent
experiments.Comment: 28 pages; 11 (main) Figs - Revtex4 - Higher resolution Figs can be
obtained upon request. To appear in Macromolecule
What antarctic plants can tell us about climate changes: Temperature as a driver for metabolic reprogramming
Global warming is strongly affecting the maritime Antarctica climate and the consequent melting of perennial snow and ice covers resulted in increased colonization by plants. Colobanthus quitensis is a vascular plant highly adapted to the harsh environmental conditions of Antarctic Peninsula and understanding how the plant is responding to global warming is a new challenging target for modern cell physiology. To this aim, we performed differential proteomic analysis on C. quitensis plants grown in natural conditions compared to plants grown for one year inside open top chambers (OTCs) which determine an increase of about 4 °C at midday, mimicking the effect of global warming. A thorough analysis of the up and downregulated proteins highlighted an extensive metabolism reprogramming leading to enhanced photoprotection and oxidative stress control as well as reduced content of cell wall components. Overall, OTCs growth seems to be advantageous for C. quitensis plants which could benefit from a better CO2 diffusion into the mesophyll and a reduced ROSâmediated photodamage
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