4 research outputs found
A Super Stable Mutant of the Plant Protein Monellin Endowed with Enhanced Sweetness
Sweet proteins are a class of proteins with the ability to elicit a sweet sensation in humans
upon interaction with sweet taste receptor T1R2/T1R3. Single-chain Monellin, MNEI, is among the
sweetest proteins known and it could replace sugar in many food and beverage recipes. Nonetheless,
its use is limited by low stability and high aggregation propensity at neutral pH. To solve this
inconvenience, we designed a new construct of MNEI, dubbed Mut9, which led to gains in both
sweetness and stability. Mut9 showed an extraordinary stability in acidic and neutral environments,
where we observed a melting temperature over 20 C higher than that of MNEI. In addition, Mut9
resulted twice as sweet than MNEI. Both proteins were extensively characterized by biophysical
and sensory analyses. Notably, Mut9 preserved its structure and function even after 10 min boiling,
with the greatest differences being observed at pH 6.8, where it remained folded and sweet, whereas
MNEI lost its structure and function. Finally, we performed a 6-month shelf-life assessment, and the
data confirmed the greater stability of the new construct in a wide range of conditions. These data
prove that Mut9 has an even greater potential for food and beverage applications than MNEI
Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care
Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42% â60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management
Frequency of Left Ventricular Hypertrophy in Non-Valvular Atrial Fibrillation
Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention
Prevalence of peripheral artery disease by abnormal ankle-brachial index in atrial fibrillation: Implications for risk and therapy
To the Editor: Nonvalvular atrial fibrillation (NVAF) is the most
common sustained arrhythmia encountered in clinical practice and
is associated with a 5-fold increased risk for stroke (1).
Moreover, patients with NVAF often suffer from atherosclerotic
complications such as acute myocardial infarction (AMI) (2).
Peripheral artery disease (PAD) is an established marker of systemic
atherosclerosis but its prevalence in NVAF is still unclear. We
reasoned that inclusion of ankle-brachial index (ABI), which is an
established tool for diagnosis of PAD (3), in the CHA2DS2-VASc
(4) score would better define the prevalence of vascular disease.
Toaddress this issue, the ItalianSociety of InternalMedicine (SIMI)
established an Italian registry documenting ABI inNVAF patients.
The Atrial Fibrillation Registry for the ARAPACIS (Ankle-
brachial Index Prevalence Assessment: Collaborative Italian Study)
study is an independent research project involving all Regional
Councils of SIMI. The first objective of the study was to estimate
the prevalence of ABI î0.90 in NVAF patients.
Consecutive patients with NVAF referred to internal medicine
wards were eligible for the enrollment. Enrollment started in
October 2010 and continued until October 30, 2012. Patients were
enrolled if they were 18 years or older and had a diagnosis of
NVAF, recording during the qualifying admission/consultation or
in the preceding 12 months, and if it was possible to obtain the
ABI measurement. Exclusion criteria included the following:
acquired or congenital valvular AF, active cancer, disease with life
expectancy <3 years, hyperthyroidism and pregnancy.
We initially planned to include 3,000 patients. The Data and
Safety Monitoring Board (Online Appendix) decided to perform an
interim analysis to assess the prevalence of ABI in the enrolled
populationsdas a higher than expected prevalence of low ABI was
detecteddand decided to interrupt the patientsâ enrollment. The
sample size was amended as follows: a sample of 2,027 patients leads
to the expected prevalence of 21% with a 95% confidence interval
width of 3.5% (StataCorp LP, College Station, Texas).
Among the 2,027 NVAF patients included in the study, hyper-
tension was detected in 83%, diabetes mellitus in 23%, dyslipidemia
in 39%, metabolic syndrome in 29%, and smoking in 15%. At least 1
atherosclerotic risk factor was detected in 90% of patients.
The NVAF population was at high risk for stroke, with only
18% having a CHA2DS2-VASc score of 0 to 1, while 82% had
a risk î2. Despite this, 16% were untreated with any antith-
rombotic drug, 19% were treated with antiplatelet drugs (APs), and
61% with oral anticoagulants (OAC); 4% of patients were treated
with both APs and OAC.
Among the AF population, 428 patients (21%) had ABI î0.90
(69%); 204 patients (10%) had ABI î1.40 (Fig. 1). ABI recorded
only in 1 leg was excluded from the analysis (n ÂŒ 14). ABI î0.90
progressively increased from paroxysmal to permanent NVAF (18%,
tensive (88% vs. 82%; p Œ 0.032), diabetic (34% vs. 20%; p <
0.0001), or smokers (20% vs. 14%; p Œ 0.0008), or to have experi-
enced transient ischemic attack or stroke (17% vs. 10%; p < 0.001).
21%, 24%; p Œ 0.0315).
NVAF patients with ABI î0.90 were more likely to be hyper-
NVAF patients with ABI î0.90 had a higher percentage of
CHA2DS2-VASc score î2 compared with those with ABI >0.90
(93% vs. 82%; p < 0.0001).
significantly associated with a smoking habit (odds ratio [OR]:
1.99; 95% confidence interval [CI]: 1.48 to 2.66; p < 0.0001),
diabetes (OR: 1.93; 95% CI: 1.51 to 2.46; p < 0.0001), age class 65
to 74 years (OR: 2.05; 95% CI: 1.40 to 3.07; p < 0.0001), age
Logistic regression analysis demonstrated that ABI î0.90 was
class î75 years (OR: 3.12; 95% CI: 2.16 to 4.61; p < 0.0001),
and history of previous transient ischemic attack/stroke (OR: 1.64;
95% CI: 1.20 to 2.24; p Œ 0.002).
Vascular disease, as assessed by the history elements of
CHA2DS2VASc score, was recorded in 17.3% of patients; inclu-
sion of ABI î0.90 in the definition of vascular disease yielded
a total prevalence of 33%. A higher prevalence of vascular disease
was detected if ABI î0.90 was included in the CHA2DS2VASc
score (Fig. 1). CHA2DS2VASc including ABI î0.90 was more
associated with previous stroke (43%; OR: 1.85; 95% CI: 1.41 to
2.44; p < 0.0001) compared to CHA2DS2VASc with ABI 0.91 to
1.39 (23%; OR: 1.52; 95% CI: 1.10 to 2.11; p Œ 0.0117).
To the best of our knowledge, there is no large-scale study that
specifically examined the prevalence of ABI î0.90 in NVAF. In
our population, 21% had ABI î0.90 indicating that NVAF is
often associated with systemic atherosclerosis.
The CHADS2 has been recently refined with the CHA2DS2-
VASc score, which includes vascular disease as documented by
a history of AMI, symptomatic PAD, or detection of atheroscle-
rotic plaque in the aortic arch (4).
Comparison of vascular prevalence as assessed by CHA2DS2-
NVAF patients. Inclusion of ABI î0.90 in the definition of
vascular disease greatly increased the prevalence of vascular disease,
which increased from 17.3% (based on history alone) to 33% (based
compared with 1,381 patients, who had an ABI of 0.91 to 1.39
to better define the risk profile ofNVAFpatients with an up-grading
of the risk score in each CHA2DS2-VASc score category. This may
have important therapeutic implications if the new score could be
tested prospectively, as a higher number of NVAF patients would
on ABI) in the entire population. If ABI î0.90 was encompassed
in the definition of vascular disease of CHA2DS2-VASc score the
prevalence of vascular disease increased in every risk class.
Inclusion of ABIî0.90 in theCHA2DS2-VASc score allowed us
VASc score and/or ABI î0.90 is of interest to define the poten-
tially positive impact of measuring ABI in the management of potentially be candidates for an anticoagulant treatment by
measuring ABI. A prospective study is, therefore, necessary to
validate the risk score of this new definition of vascular disease.
In conclusion, this study provides the first evidence that one-fifth
of NVAF patients had an ABI î0.90, indicating that it may
represent a simple and cheap method to better define the prevalence
of vascular disease in NVAF