153 research outputs found
"Pelvic ultrasound evaluation in transgender male during testosterone therapy" G. Senofonte, E. Marcoccia, C. Boccherini, M. Marasco, A. Perlorca, G. Nigro, A. Giancotti, M. Mosconi, F. Lombardo
No full textIntroduction: Gender dysphoria (GD) is characterised by significant distress and/or poor
social functioning due to a non-congruence between an individual’s assigned gender and the
perceived gender identity. In Female to Male subjects, androgen therapy aims to induce
physical changes (such as hair growth, tone voice decrease, fat mass redistribution, breast
volume reduction, etc) and cessation of menses. The latest guidelines (Hembree, 2017)
suggest a higher risk of malignancies (uterus and ovaries) and of endometrial hyperplasia than
cis-gender female, secondary to testosterone therapy. Therefore, a radical
hysteroannesisectomy is recommended after 2 years of therapy.
Aims: The aim of this study is the acquisition of data from pelvic ultrasound surveillance in
Transgender Male in order to evaluate endometrial thickness, uterine and ovarian volume.
Materials and Methods: FtM subjects referred to the outpatient clinic of Endocrinology and
Andrology of the Department of Experimental Medicine, “Sapienza” University of Rome, for
Gender Dysphoria, sent by their mental health specialists. We recruited 26 patients (mean age
27.3 ± 11.0) with the following inclusions criteria: diagnosis of gender dysphoria, participation
on follow-up, no previous testosterone therapy; exclusions criteria were: history of
gynaecological surgery/hysterectomy, menopause. Each patient underwent clinical
evaluation, blood testosterone test and US evaluation before starting therapy (T0) and after
six months of therapy (T 6). The hormone therapy consisted of intramuscolar testosterone
undecanoate 250 mg-every 28 days.
Results: Twenty-six subjects underwent the baseline evaluation: mean uterine volume was
49.4 ± 21.7 cc, mean endometrial thickness was 5.0 ± 3.5 mm, mean right ovarian volume was
5.9 ± 5.3 cc, mean left ovarian volume was 7.5 ± 6.8 cc and mean endometrial thickness was
5.0 ± 3.5 mm. At this time, 12 patients finished six months therapy and returned for control.
The cessation of menses occurred in all patients after a median of 2 months (approximately 2
testosterone undecanoate injections). There was no significant difference in post therapy
mean uterine volume (49.4 ± 21.7 cc vs 49.9 ± 29.0 cc, T0 vs T6, p = 0.43) and in endometrial
thickness (5.0 ± 3.5 mm vs 2.7 ± 1.0 mm, T0 vs T6, p = 0.15). Instead we detected a significant
decrease in mean left ovarian volume (7.5 ± 6.8 cc vs 2.7 ± 1.1, T0 vs T6, p = 0.002) and right
ovarian volume (5.9 ± 5.3 cc vs 2.3 ± 1.7, T0 vs T6, p =0.010). Blood tests confirmed a
significant increase of testosterone levels after six months of therapy (1.3 ± 0.9 vs 13.4 ± 4.5
nnmol/L, T0 vs T6; p=0.001). We did not detect any significant correlation between
testosterone levels under treatment and ovarian volume.
Conclusions: Testosterone therapy induces marked physical changes, as demonstrated by
menses cessation and reduction of ovarian volume, although apparently not correlated with
mean blood testosterone level. No significant difference were found in endometrial thickness
and uterine volume, though these results may be due in part to the small number of enrolled
subjects. Future increase of study cohort and longer follow up will strengthen our results and
possibly provide information on risk of malignancies in trangender males
Exploring the role of L209 residue in the active site of NDM-1 a metallo-β-lactamase
No full textBackground & para;& para;New Delhi Metallo-beta-Lactamase (NDM-1) is one of the most recent additions to the beta-lactamases family. Since its discovery in 2009, NDM-1 producing Enterobacteriaceae have disseminated globally. With few effective antibiotics against NDM-1 producers, there is an urgent need to design new drug inhibitors through the help of structural and mechanistic information available from mutagenic studies.& para;& para;Results/Conclusions & para;& para;In our study we focus the attention on the non-catalytic residue Leucine 209 by changing it into a Phenylalanine. The L209F laboratory variant of NDM-1 displays a drastic reduction of catalytic efficiency (due to low k(cat) values) towards penicillins, cephalosporins and carbapenems. Thermofluor-based assay demonstrated that NDM-1 and L209F are stable to the temperature and the zinc content is the same in both enzymes as demonstrated by experiments with PAR in the presence of GdnHCL. Molecular Dynamics (MDs) simulations, carried out on NDM-1 and L209F both complexed and uncomplexed with Benzylpenicillin indicate that the point mutation produces a significant mechanical destabilization of the enzyme and also an increase of water content. These observations clearly show that the single mutation induces drastic changes in the enzyme properties which can be related to the observed different catalytic behavior
STRATEGIE DI CONSERVAZIONE IN SITU ED EX SITU DI BIDENS CERNUA L., SPECIE MINACCIATA NEL LAZIO.
No full textThe Concept of Early Systemic Sclerosis Following 2013 ACR\EULAR Criteria for the Classification of Systemic Sclerosis.
No full textThe role of calcium carbonate in the geomechanical behaviour of Pliocene lacustrine deposits.
No full textThe results of a study on the influence of calcium carbonate content on the physical characteristics and compressibility parameters of Pliocene lacustrine deposits are discussed. The origin of CaCO3 has been investigated and it is thought to have been precipitated, after consolidation, as cement which partially filled the void spaces between soil particles. Average CaCO3 content was about 22% along a 116.5 m deep vertical profile. The CaCO3 in the clay and silt fractions (CaCO3*) was considered the best available estimate of that acting as cement. The relationships reported in the literature between Atterberg limits and CaCO3 content have been statistically confirmed by the tests performed on decalcified laboratory samples, but not by those performed on natural samples due to lithological heterogeneities. Yield stress, constrained modulus, swelling index and microstructure resistance were affected by CaCO3* content in the stress range lower than yield stress. In the stress range higher than sigma'(vy), no relationship was observed between C-c and CaCO3, while an inverse relationship between C-s and CaCO, was observed in both the natural and remoulded samples and thus is thought to be due to the presence of inactive calcite. Moreover, the remoulded samples also show an increase in C-s with respect to the natural ones. From these findings it follows that the yield stress for cemented materials corresponds to the partial disruption of the structure
Signal analysis in gravitational wave data
No full textIn this thesis, I study the gravitational wave signals coming from compact objects on both present-stage, and future gravitational wave detectors.
The thesis is based on 3 articles, which will be presented after two brief introductory chapters, aimed to guide the reader through some of the main concepts and tools required in the analysis of the presented papers.
In the first article we adopt the Pearson Cross-Correlation analysis, to perform an agnostic search on real detector data of the first four LIGO gravitational wave detections. This work was motivated as a follow-up to some studies carried out by a group at the Niels-Bohr Institute. In their works, they tried to reproduce the detections claimed by the LIGO collaboration using matched filtering, and they discovered that the waveforms used by the LIGO collaboration in their subtractions were not optimal, as some of the signal remained buried in the detector noise after the subtraction. In the paper we used different waveforms, obtained through maximum-likelihood, and we demonstrate that the residual signal found in the noise was just a consequence of the choice of waveforms. Such signal, buried in the residual detector noise, is hence not a result of mismatching on the model but can be removed by using a more accurate waveform description. Furthermore, we show that the LIGO results can be reproduced with statistical significance even by using the Pearson cross-correlation method, even though with this approach the statistical significance will be slightly lower compared to the results obtained using matched filtering.
For the second article we moved to the case of simulated signals, coming from many events, on a future space-based detector datastream. To this extent we analyze the Stochastic Gravitational Wave Background predicted on the LISA detector, which is given by the superposition of all the weak unresolvable signals on the detector strain. We forecast the signal on the LISA detector strain by using the results coming from the latest LVK population inference paper, and produced catalogs representing a Stellar-Origin Black Hole population in our Universe. The Stochastic Gravitational Wave Background is then computed by adopting four different methods, that in order of complexity, range from a simple analytical evaluation to estimating the real detector strain after synthesizing a black hole population and iteratively subtracting all the resolvable sources. We find that, when the assumed SNR threshold is high enough to keep the number of resolvable sources small (∼ 10 over 4 years of observation), all the methods give results well in agreement with each other. This implies that, when working with LISA data, it is possible to use the fast analytical estimation for the stochastic noise component with a small loss of precision. On the other hand, the use of more complex methods like the iterative subtraction of a synthesized population, despite naturally requiring numerical cuts in the population generation phase due to its computational cost, can present both the value of the Stochastic Gravitational Wave Background amplitude as well as the resolvable sources predicted on the LISA strain at the same time. It can hence be useful when both these quantities need to be taken into account in a particular study.
We conclude on the third article by studying the synergy of multiple future gravitational wave detectors (both Earth-based and Space-based), in assessing the presence of secondary population channels in the detectors data stream. To this extent, we investigate the prospects of identifying potential Primordial Black Hole Binary populations over the astrophysical Stellar-Origin Black Hole Binary population of our Universe. We once again assume that our fiducial population follows the latest LVK GWTC-3 inference paper results, and we forecast our analysis on the next generation of gravitational wave detectors. We consider different possibilities both for the merger rate and mass function of the studied Primordial Black Hole subpopulations, and we perform our analysis by focusing on the signatures at higher redshifts than the current LVK detection horizon. We exploit the fact that the astrophysical black holes of our universe are supposed to follow a distribution as a function of redshift closely related to the Star Formation Rate, which is supposed to peak and then slowly die off. At distances beyond the peak of the stellar formation rate, the Stellar-Origin Binary Black Hole contribution will hence become negligible, whereas Primordial Black Hole models predict many sources and will dominate. We generally find that Earth-based and space-based detectors work synergistically, and the value of the Stochastic Gravitational Wave Background measured by LISA will generally be able to improve constraining the presence of additional sub-populations compared to the case when only Earth-based detector observations are considered
A Kinetic Study of the Replacement by Site Saturation Mutagenesis of Residue 119 in NDM-1 Metallo- beta-Lactamase
No full textpeer reviewedNew Delhi metallo- beta-lactamase 1 (NDM-1) is a subclass B1 metallo-beta -
lactamase that exhibits a broad spectrum of activity against beta -lactam antibiotics. Here
we report the kinetic study of 6 Q119X variants obtained by site-directed mutagenesis
of NDM-1. All Q119X variants were able to hydrolyze carbapenems, penicillins and first-,
second-, third-, and fourth-generation cephalosporins very efficiently. In particular,
Q119E, Q119Y, Q119V, and Q119K mutants showed improvements in kcat/Km values for
penicillins, compared with NDM-1. The catalytic efficiencies of the Q119K variant for
benzylpenicillin and carbenicillin were about 65- and 70-fold higher, respectively, than
those of NDM-1. The Q119K and Q119Y enzymes had kcat/Km values for ceftazidime
about 25- and 89-fold higher, respectively, than that of NDM-1
Interaction of carbapenems and β-lactamase inhibitors towards CTX-M-15 and CTX-M-15 G238C mutant
No full textObjectives: The aim of this study was to evaluate the role of residue
238 in CTX-M-15 and CTX-M-15(G238C) mutant with respect to carbapenems
and various beta-lactamase inhibitors.
Methods: A CTX-M-15(G238C) laboratory mutant was generated by
site-directed mutagenesis from CTX-M-15 enzyme by replacing glycine 238
with cysteine. Thiol titration and p-chloromercuribenzoate (PCMB)
inactivation assays were used to ascertain the presence of a disulfide
bridge in the active site of CTX-M15(G238C). Kinetic parameters were
determined both for CTX-M-15 and CTX-M-15(G238C) enzymes by analysing
either the complete hydrolysis time courses or under initial rate
conditions.
Results: In CTX-M-15(G238C) mutant, the two cysteines (C69 and C238)
located in the enzyme active site were unable to form a disulfide
bridge. CTX-M-15 and thermostable CTX-M-15(G238C) were used to study the
kinetic interaction with carbapenems, which behaved as poor substrates
for both enzymes. Meropenem and ertapenem acted as transient
inactivators for CTX-M-15 and CTX-M-15(G238C), and for these compounds
the variation of k(obs) versus the inactivator concentration was linear.
Imipenem behaved as a transient inactivator for CTX-M-15 and as an
inactivator (with k(+3) = 0) for CTX-M-15(G238C). In any case, the
k(+2)/K values for CTX-M-15(G238C) were higher than those for CTX-M-15.
Conclusions: Compared with CTX-M-15, CTX-M-15(G238C) mutant appears to
have a more favourable conformation for carbapenem acylation and higher
activity against cefotaxime, which could be due to the presence of free
-SH groups in the enzyme active site.100950,6582,022Q2Q3SCI
Chronic abdominal pain associated with intermittent compression of the celiac artery
No full textRecurrent abdominal pain (RAP), surely one of the most frequent causes of medical intervention, is frequently present in many gastrointestinal disease. Usually no structural and/or biochemical alterations can be demonstrated. This condition is, therefore, considered to be due to functional disorders such as irritable bowel syndrome (IBS) or functional dyspepsia. Previous observations suggest the presence of a rare alteration of celiac vessels among the possible causes of RAP. This pathological condition was known as Dunbar syndrome. We report 2 cases of chronic abdominal pain. The former reported weight loss and the latter anemia with iron deficiency. It is remarkable that patients with initial diagnosis of IBS can be affected by celiac disease (CD), which is the cause of their abdominal pain. Our patients were tested for CD; the former was negative and IBS was diagnosed, the latter was positive and a gluten free diet was prescribed. The presence of an epigastric bruit, accentuated during expiration, suggested a possible vascular alteration known as tripod celiac artery compression syndrome. Duplex Doppler sonography suggests the diagnosis of celiac arterial constriction due the diaphragmatic ligament. These cases show that tripod celiac artery compression syndrome might be a cause of RAP and that it may be evaluated and investigated when the clinical examination discloses an abdominal systolic bruit
Early Systemic Sclerosis: Marker Autoantibody Positive Patients Have A Faster Pace Of The Disease.
No full textEarly Systemic Sclerosis: Marker Autoantibody Positive Patients Have A Faster Pace Of The Disease.
Background/Purpose: To investigate whether patients affected with any of the 3 subsets of early systemic sclerosis (SSc) i.e. Raynaud’s Phenomenon (RP) with SSc marker autoantibody (ACA or anti-Scl70 or anti-RNA polymerase III or anti-fibrillarin or anti-Th/To) and typical capillaroscopic findings (megacapillaries and/or avascular areas) (subset I); or autoantibody positive only (subset II); or capillaroscopy positive only (subset III) (1) and unsatisfying the 2012 ACR/EULAR classification criteria for SSc (2) at admission differ in the lag time to satisfy the new SSc classification criteria. Methods: Early SSc patients consecutively admitted to a Rheumatology and an Angiology center and unsatisfying the 2012 ACR/EULAR classification criteria for SSc at admission, were subdivided into the 3 above referred subsets and followed-up for 7–101 months (median 45). S288 Sunday, October 27 They were re-evaluated six-monthly by history, clinical examination, B-mode echoDopplercardiography and Lung functional study including DLCO evaluation and yearly by lung HRCT to assess whether and when each of them satisfied new ACR/EULAR classification criteria i.e. developed a disease score 9 (2). Results: During the follow-up, 11 out of 21 subset I patients (52.3%) (baseline score 8); 10 out of 15 subset II patients (66.6%) (baseline score 6) and 0 out of 24 subset III patients (baseline score 5–7) satisfied the criteria; the difference being significant between each of the 2 autoantibody positive (subsets I and II) and the capillaroscopic positive-autoantibody negative subset (subset I versus III: X2 by log rank test17.45, p0.0001; subset II versus III: X2 11.04, p0.0009), no difference being detected between the 2 autoantibody positive subsets (X2 0.55, p0.454). The 11 subset I patients satisfied the criteria because of the development of teleangectasias in 5 cases; puffy fingers in 3 cases; lung fibrosis in 2 cases; digital ulcers in 1 case. The 10 subset II patients did it because of the development of at least 2 of the following manifestations: scleroderma capillaroscopic pattern in 5 cases, teleangectasias in 5 cases, puffy fingers in 5 cases, digital ulcers in 3 cases, pulmonary hypertension in 1 case and lung fibrosis in 1 case. Despite the unfulfillment of the criteria, among the 24 subset III patients, 21 of whom already presented puffy fingers at baseline, 2 developed telangectasias, 1 digital ulcers, 4 a DLCO 80%. Conclusion: We have recently pointed out that autoantibody positive early SSc patients differ from subset III patients in the pattern of activation markers (increased serum concentration of procollagen I carbossipropeptide versus increased serum concentration of E-selectin) and preclinical internal organ involvement (higher prevalence of decreased DLCO) (3). Here we point out that autoantibody positive patients present a faster pace of the disease. References: 1) Koenig M et al. Arthritis Rheum. 2008;58:3902–12 2) Van den Hoogen F et al. Eular Congress 2013, OP0033 3) Valentini G et al. Arthritis Res Ther. 2013; 29;15:R63 Disclos
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