The role of family history of preterm delivery in the individual risk of spontaneous preterm delivery: a case-control study.

PURPOSE: To investigate the role of family history of preterm delivery (PTD) in the individual risk of spontaneous preterm delivery. METHODS: A retrospective case-control study was conducted on 354 patients who delivered between 2018 and 2020. 177 women who delivered preterm were matched with 177 controls who had full-term delivery. A questionnaire was administered to investigate the family history of PTD of both the patient and her partner. Cases and controls were matched for the anamnestic risk factors for PTD. RESULTS: Seventeen of 173 women (9.8%) in the PTD group reported being born preterm, compared to five of 169 women (2.9%) in the control group (p = 0.01), with an odds ratio (OR) of 3.57 (95% confidence interval, CI 1.29-9.92). Women who delivered preterm also reported more frequently having a sibling who was born preterm (12.4% vs. 4.2%, p = 0.01), with an OR of 3.18 (95% CI 1.31-7.7). No association was found between the partner's family history of premature delivery and the patient's risk of preterm delivery in the present pregnancy. CONCLUSIONS: Pregnant patients who were born prematurely or who have siblings born preterm have an increased risk of preterm delivery in their own pregnancies. Assessment of female personal and family history of PTD should be used to identify women at risk of having a PTD in the present pregnancy.

Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism.

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.

Abacavir has no prothrombotic effect on platelets in vitro.

OBJECTIVES: HIV patients exposed to abacavir have an increased risk of myocardial infarction, with contradictory results in the literature. The aim of our study was to determine whether abacavir has a direct effect on platelet activation and aggregation using platelets from healthy donors and from HIV-infected patients under therapy with an undetectable viral load. METHODS: Platelet-rich plasma (PRP) or whole blood from healthy donors was treated with abacavir (5 or 10 µg/mL) or its active metabolite carbovir diphosphate. Experiments were also performed using blood of HIV-infected patients (n = 10) with an undetectable viral load. Platelet aggregation was performed on PRP by turbidimetry and under high shear conditions at 4000 s-1. Platelet procoagulant potential was analysed by measuring thrombin generation by thrombinography. RESULTS: Abacavir and carbovir diphosphate significantly increased the aggregation of platelets from healthy donors induced by collagen at 2 µg/mL (P = 0.002), but not at 0.5 µg/mL. No effect of abacavir or carbovir diphosphate was observed on platelet aggregation induced by other physiological agonists or by high shear stress, or on thrombin generation. Pretreatment of blood from HIV-infected patients with abacavir produced similar results. CONCLUSIONS: Our results suggest that abacavir does not significantly influence platelet activation in vitro when incubated with platelets from healthy donors or from HIV-infected patients. It is, however, not excluded that a synergistic effect with other drugs could promote platelet activation and thereby play a role in the pathogenesis of myocardial infarction.

Torcetrapib differentially modulates the biological activities of HDL2 and HDL3 particles in the reverse cholesterol transport pathway.

OBJECTIVE: Therapeutic strategies to raise low plasma HDL-cholesterol levels, with concomitant normalization of the intravascular metabolism, physicochemical properties, and antiatherogenic function of HDL particles, are a major focus in atherosclerosis prevention. METHODS AND RESULTS: Patients displaying Type IIB hyperlipidemia (n=14) and healthy controls (n=11) were recruited. After drug washout, dyslipidemic patients first received atorvastatin (10 mg/d) for 6 weeks and subsequently torcetrapib/atorvastatin (60/10 mg/d) for the same period. Partial CETP inhibition markedly reduced supranormal CE transfer rates to normal levels from HDL3 (-58%; P<0.0001) to apoB-lipoproteins; endogenous CE transfer rates from HDL2 to apoB-lipoproteins were markedly subnormal as compared to those in control subjects (10.7+/-0.9 versus 29.3+/-4.8 microg CE/h/mL plasma, respectively). Torcetrapib enhanced the subnormal capacity of HDL2 particles from dyslipidemic patients to mediate free cholesterol efflux via both SR-BI and ABCG1 pathways (+38%; P<0.003 and +35%; P<0.03, respectively) as compared to baseline. In vitro observations and in vivo studies in mice demonstrated that CETP inhibition was associated with an enhanced selective hepatic uptake of CE from HDL particles (1.7-fold; P<0.0003). CONCLUSIONS: CETP inhibition partially corrected the abnormal physicochemical and functional properties of HDL2 and HDL3 particles in type IIB hyperlipidemia. Enhanced hepatic selective uptake of HDL-CE may compensate for attenuated indirect CE transfer to apoB-containing lipoproteins via CETP attributable to torcetrapib.

Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects.

We evaluated the impact of gender differences in both the quantitative and qualitative features of HDL subspecies on cellular free cholesterol efflux through the scavenger receptor class B type I (SR-BI), ABCA1, and ABCG1 pathways. For that purpose, healthy subjects (30 men and 26 women) matched for age, body mass index, triglyceride, apolipoprotein A-I, and high density lipoprotein-cholesterol (HDL-C) levels were recruited. We observed a significant increase (+14%; P < 0.03) in the capacity of whole sera from women to mediate cellular free cholesterol efflux via the SR-BI-dependent pathway compared with sera from men. Such enhanced efflux capacity resulted from a significant increase in plasma levels of large cholesteryl ester-rich HDL2 particles (+20%; P < 0.04) as well as from an enhanced capacity (+14%; P < 0.03) of these particles to mediate cellular free cholesterol efflux via SR-BI. By contrast, plasma from men displayed an enhanced free cholesterol efflux capacity (+31%; P < 0.001) via the ABCA1 transporter pathway compared with that from women, which resulted from a 2.4-fold increase in the plasma level of prebeta particles (P < 0.008). Moreover, in women, SR-BI-mediated cellular free cholesterol efflux was significantly correlated with plasma HDL-C (r = 0.72, P < 0.0001), whereas this relationship was not observed in men. In conclusion, HDL-C level may not represent the absolute indicator of the efficiency of the initial step of the reverse cholesterol transport.