Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10 % of women of reproductive age. It generally manifests with oligo/anovulatory cycles, hirsutism and polycystic ovaries, ...together with a considerable prevalence of insulin resistance. Although the aetiology of the syndrome is not completely understood yet, PCOS is considered a multifactorial disorder with various genetic, endocrine and environmental abnormalities. Moreover, PCOS patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10% of women of reproductive age. It generally shows with oligo/amenorrhea, anovulatory cycles, clinical o biochemical ...hirsutism, polycystic ovaries and, in a significant percentage of cases, insulin resistance. PCOS is defined as a multifactorial pathology, determined by the association of many factors: genetic, endocrine and environmental.
The first and most effective treatment of PCOS is to change life-style and lose weight. The use of oral contraceptives has been shown effective in reducing acne and hirsutism and regulates the menstrual cycle. For women with severe hirsutism, the addition of antiandrogens to estrogen-progestin therapy has significantly improved the results. In cases of anovulatory infertility, the drug of first choice is clomiphene citrate, followed by low-dose gonadotropins. Recently, insulin-sensitizing drugs have been widely prescribed for PCOS patients. They are particularly effective in reducing insulin resistance and improving ovulatory performance. Besides insulin-sensitizing drugs, natural substances, such as inositol, seems to have good efficacy, similar to metformin with fewer side effects. New substances that could be used include statins and natural statins, such as monakolin, alone or combined with myo-inositol. These substances do not have side effects and greatly reduce the hyperandrogenic component in these patients.
A
bstract
The quantum interference between the decays of entangled neutral kaons is studied in the process
ϕ
→ K
S
K
L
→
π
+
π
−
π
+
π
−
, which exhibits the characteristic Einstein-Podolsky-Rosen ...correlations that prevent both kaons to decay into
π
+
π
−
at the same time. This constitutes a very powerful tool for testing at the utmost precision the quantum coherence of the entangled kaon pair state, and to search for tiny decoherence and
CPT
violation effects, which may be justified in a quantum gravity framework.
The analysed data sample was collected with the KLOE detector at DAΦNE, the Frascati
ϕ
-factory, and corresponds to an integrated luminosity of about 1.7 fb
−
1
, i.e. to about 1
.
7 × 10
9
ϕ
→ K
S
K
L
decays produced. From the fit of the observed ∆
t
distribution, being ∆
t
the difference of the kaon decay times, the decoherence and
CPT
violation parameters of various phenomenological models are measured with a largely improved accuracy with respect to previous analyses.
The results are consistent with no deviation from quantum mechanics and
CPT
symmetry, while for some parameters the precision reaches the interesting level at which — in the most optimistic scenarios — quantum gravity effects might show up. They provide the most stringent limits up to date on the considered models.
Abstract
STUDY QUESTION
Are cohesins SA1/SA2 and the NAD-dependent deacetylase SIRT1 involved in telomere homeostasis of cumulus cells and thus eligible as biomarkers of follicular physiology and ...ovarian aging?
SUMMARY ANSWER
SA1/SA2 cohesins and SIRT1 are associated with telomere length in cumulus cells and may be eligible biomarkers of follicular physiology and ovarian aging.
WHAT IS KNOWN ALREADY
In somatic cells, cohesins SA1/SA2 mediate sister chromatid cohesion at the telomere termini (for SA1) and along chromatid arms (for SA2). The NAD+-dependent protein deacetylase Sirtuin 1 (SIRT1), which preserves DNA integrity from oxidative stress, may also modulate genome stability and telomere length.
STUDY DESIGN, SIZE, DURATION
Collectively 280 cumulus/oocyte complex samples were recovered from a total of 50 women undergoing in vitro fertilization.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Cumulus cells were separated from the oocyte-cumulus complex. DNA and total mRNA were extracted from cumulus cells and assayed for telomere length and for SA1, SA2 and SIRT1 gene expression profiling. Telomere length was determined by quantitave PCR and analyzed relative to the single copy of the housekeeping gene (albumin) to generate a T/S ratio (Telomere/single copy gene). Gene expression levels of SA1, SA2 and SIRT1 mRNA were assayed by quantitative RT-PCR and confirmed by western blotting and immunofluorescent studies (SIRT1). SA1/SA2 and SIRT1 gene expression levels and telomere length analysis of patients/samples were ranked in relation to their clinical setting parameters (BMI, age) and to the number of oocyte retrieved.
MAIN RESULTS AND THE ROLE OF CHANCE
SA1 and SA2 transcripts were both detected in all cumulus cells analyzed and the relative amount showed a clear decreasing trend according to the age of patients. A significant increase in SA1 and SA2 was disclosed in high responder women (>6 oocytes retrieved) compared to poor responders (<4 oocytes) (P < 0.05). Furthermore, statistically significant positive correlations were also recorded between the transcripts levels of the two cohesin molecules (r = 0.89; P < 0.05) and, to a lesser extent, between telomere length and SA1 (r = 0.42; P < 0.001) and SA2 (r = 0.36; P < 0.001) mRNA levels. SIRT1 expression was also significantly increased in high responders (>6 oocytes) compared to poor responders. Significant correlations were found between SIRT1 and SA1 (r = 0.69; P < 0.001), between SIRT1 and SA2 (r = 0.78; P < 0.001), and between SIRT1 and telomere length (r = 0.36; P < 0.001). However, in the older patient group (>38 years), SIRT1 mRNA levels were twice as high as the levels recorded in the younger patient cohort (<34 years). Western blot analysis and immunofluorescent studies confirmed the increments in SIRT1 protein levels in patients over 38 years old.
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
Cumulus/oocyte complexes were retrieved by patients undergoing ovarian stimulation protocol for IVF. We cannot exclude the possibility that different stimulation protocols affect the correlations highlighted in this study. Future investigations should shed light on cumulus cells molecular profile according to different stimulation protocols.
WIDER IMPLICATIONS OF THE FINDINGS
The overall results of our study point to the involvement of cohesins SA1/SA2 and SIRT1 deacetylase in telomere homeostasis in cumulus cells and highlight their possible eligibility as biomarkers of follicular physiology and ovarian aging.
STUDY FUNDING/COMPETING INTEREST(S)
Merck Serono S.P.A Italy sponsored the study with financial support. There are no competing interests to declare.
A
bstract
The ratio
R
= Γ(
K
S
→ πeν
)
/
Γ(
K
S
→ π
+
π
−
) has been measured with a sample of 300 million
K
S
mesons produced in
ϕ → K
L
K
S
decays recorded by the KLOE experiment at the DAΦNE
e
+
e
...−
collider.
K
S
→ πeν
events are selected by a boosted decision tree built with kinematic variables and time-of-flight measurements. Data control samples of
K
L
→ πeν
decays are used to evaluate signal selection efficiencies. With 49647
±
316 signal events we measure
R
= (1
.
0421
±
0
.
0066
stat
±
0
.
0075
syst
)
×
10
−
3
. The combination with our previous measurement gives
R
= (1
.
0338
±
0
.
0054
stat
±
0
.
0064
syst
)
×
10
−
3
. From this value we derive the branching fraction
B
(
K
S
→ πeν
) = (7
.
153
±
0
.
037
stat
±
0
.
044
syst
)
×
10
−
4
and
f
+
(0)
|V
us
|
= 0
.
2170
±
0
.
009.
PCOS is the most common endocrinopathy among reproductive age women. Approximately 60% of PCOS women have insulin resistance. While the efficacy of metformin in reducing insulin resistance and ...decreasing androgen level has been widely validated, there is no agreement on the dose of metformin to be used.
Prospective non-randomized cohort study of 108 insulin resistant, overweight and obese PCOS women, aged between 22 and 35 years. All patients received 1500 mg of metformin (500 mg x 3 times/day) for the first 6 months. At the end of this period, the patients' HOMA index was evaluated. In subjects, who did not demonstrate normalization of the HOMA index, the dose was increased to 2500 mg/day (500 mg at breakfast and 1000 mg at lunch and dinner) for additional 6 months. The hormonal blood profile, fasting insulin and fasting glucose levels, HOMA index, anthropometric assessment, pelvic ultrasound, FAI index and cholesterol were evaluated.
Overall results showed a good response to metformin therapy in insulin-resistant PCOS patients with BMI >25, while in patients with higher BMI (31.15 ± 0.40), no normalization of HOMA was found. At the higher dose of metformin, obese patients achieved a good response to therapy, with improvement in BMI, menstrual pattern, cholesterol levels and hyperandrogenism.
Our results demonstrate a correlation between the required dose of metformin, BMI and hyperandrogenism. The dose of metformin should be adjusted to patients' BMI in order to obtain significant results in terms of clinical, metabolic and hormonal responses.
Neutral kaon pairs produced in ϕ decays in anti-symmetric entangled state can be exploited to search for violation of CPT symmetry and Lorentz invariance. We present an analysis of the CP-violating ...process ϕ→KSKL→π+π−π+π− based on 1.7 fb−1 of data collected by the KLOE experiment at the Frascati ϕ-factory DAΦNE. The data are used to perform a measurement of the CPT-violating parameters Δaμ for neutral kaons in the context of the Standard Model Extension framework. The parameters measured in the reference frame of the fixed stars are:Δa0=(−6.0±7.7stat±3.1syst)×10−18 GeV,ΔaX=(0.9±1.5stat±0.6syst)×10−18 GeV,ΔaY=(−2.0±1.5stat±0.5syst)×10−18 GeV,ΔaZ=(3.1±1.7stat±0.5syst)×10−18 GeV. These are presently the most precise measurements in the quark sector of the Standard Model Extension.
The Italian Society of Contraception identified as one of its priorities the need to give recommendations on management of contraception during Coronavirus-Covid 19 pandemia
A concise communication ...was produced which summarises in an easy-to-read format suitable for clinicians the management of the different contraceptives mostly used. Information how to manage contraception in different conditions is presented.
Women may, in general, continue to use either intrauterine and or hormonal contraceptives. The use of condom should be added to any hormonal contraceptive, when the contraceptive efficacy is reduced or when women stop the contraceptive method.
At the present time, during the Coronavirus-Covid 19 pandemia, no data contraindicate the use of intrauterine or hormonal contraceptives. Conversely the use of an appropriate contraception is advocate to prevent unintended pregnancies.
Purpose
The purpose of this study was to evaluate the oxidative stress status (OS) of follicular fluid (FF) and the oocyte quality in women with polycystic ovary syndrome (PCOS) undergoing different ...ovarian stimulation protocols.
Methods
FF samples were collected after gonadotropin administration in association or not with metformin or D-chiro-inositol (DCI). OS status was then evaluated by checking the follicular fluid protein oxidation profile after specific labeling of aminoacidic free–SH groups, and two-dimensional electrophoresis followed by qualitative and semiquantitative analysis. Oocyte quality was assessed by international morphological criteria.
Results
Our data indicated that both treatments, even if to different extent, recovered a significantly high level of free–SH groups in FF proteins of PCOS women clearly indicating a decrease of OS level with respect to that found in FF samples from gonadotropins alone treated women. A higher number of good quality MII oocytes was also observed in DCI (
P
< 0.05) or metformin (
P
< 0.05) study groups in comparison to untreated control group.
Conclusion
A natural supplement and a drug both showed a statistically significant positive effect on follicular milieu by decreasing the oxidative damage on FF proteins, as well as in recovering good quality oocytes.
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