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Background: Oxytocin is effective in reducing labor duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labor. We assessed the impact of discontinuing oxytocin during active labor on neonatal morbidity. Methods: STOPOXY was a multicenter, randomized, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4cm dilation were randomly assigned, in a 1:1 ratio to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6cm) or continuous oxytocin (administration of oxytocin is continued until delivery). Randomization was stratified by center and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth <7.10 and/or a base excess >10mmol/L and/or umbilical arterial lactates>7 mmol/L and/or a 5-minute Apgar score <7 and/or admission in neonatal intensive care unit. Results: Out of the 2459 participants randomized between January 13, 2020, and January 24, 2022, 2170 were eligible to receive the intervention and were analyzed. The primary outcome occurred in 102 of 1067 women (9.6%, 95%CI(7.9 to 11.5)) in the discontinuous oxytocin group and in 101 of 1103 women (9.2%, 95%CI(7.6 to 11.0)) in the control group, absolute difference 0.004, 95%CI(-0.021 to 0.029); RR 1.0, 95%CI(0.8 to 1.4). There were no clinically significant differences in adverse events between the two groups of the safety population. Interpretation: Among participants receiving oxytocin in early labor, discontinuing oxytocin when active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared to continuous oxytocin.

Background Elderly patients are at high-risk of bleeding, but are under-represented in clinical trials. Objectives The aims were to determine the incidence and the predictive factors of bleeding and to assess the impact of bleeding on further ischemic outcomes in elderly patients after acute coronary syndrome (ACS) treated with percutaneous coronary intervention. Methods From the 877 patients aged ≥ 75 years included in the ANTARCTIC randomized trial, data on Bleeding Academic Research Consortium (BARC) bleeding complications and major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, and stroke, were collected over 1 year. Results Clinically relevant bleeding events (BARC types 2, 3, or 5) were observed in 20.6% of patients ( n  = 181) at 1 year, of which, one third occurred in the first month. Anemia (adjusted hazard ratio [adj.HR] 3.98, 95% confidence interval [CI] 1.41–11.22; p  = 0.009), severe chronic renal failure (adj.HR 1.83, 95% CI 1.12–2.98; p  = 0.015), and femoral access (adj.HR 2.54, 95% CI 1.71–3.77; p  < 0.001) were independently associated with clinically relevant bleeding events, while age > 85 years (adj.HR 2.22, 95% CI 1.14–4.30; p  = 0.018) was independently associated with major bleeding events (BARC types 3 or 5). Patients with a clinically relevant bleeding event had a higher rate of MACE at 1 year (adj.HR 2.04, 95% CI 1.24–3.38; p  = 0.005), with a particularly strong effect on stroke (adj.HR 5.55, 95% CI 2.04–15.06; p  < 0.001). Conclusions Clinically relevant bleeding events were observed in one out of five elderly patients undergoing stenting for an ACS and were strongly associated with further stroke occurrence. Rather than the antiplatelet therapy, comorbidities and an age > 85 years predicted bleeding outcomes in this elderly population. Clinical Trial Registration Clinicaltrials.gov identifier: NCT01538446. https://www.clinicaltrials.gov .

Although autografts are considered to be the gold standard treatment for reconstruction of large bone defects resulting from trauma or diseases, donor site morbidity and limited availability restrict their use. Successful bone repair also depends on sufficient vascularization and to address this challenge, novel strategies focus on the development of vascularized biomaterial scaffolds. This pilot study aimed to investigate the feasibility of regenerating large bone defects in sheep using 3D-printed customized calcium phosphate scaffolds with or without surgical vascularization. Pre-operative computed tomography scans were performed to visualize the metatarsus and vasculature and to fabricate customized scaffolds and surgical guides by 3D printing. Critical-sized segmental defects created in the mid-diaphyseal region of the metatarsus were either left empty or treated with the 3D scaffold alone or in combination with an axial vascular pedicle. Bone regeneration was evaluated 1, 2 and 3 months post-implantation. After 3 months, the untreated defect remained non-bridged while the 3D scaffold guided bone regeneration. The presence of the vascular pedicle further enhanced bone formation. Histology confirmed bone growth inside the porous 3D scaffolds with or without vascular pedicle inclusion. Taken together, this pilot study demonstrated the feasibility of precised pre-surgical planning and reconstruction of large bone defects with 3D-printed personalized scaffolds.

A series of novel 2,9-bis[(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological results showed antiprotozoal activity with IC50 values in the sub and μM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The substituted diphenylphenanthroline 1l was identified as the most potent antimalarial derivative with a ratio of cytotoxic to antiparasitic activities of 505.7 against the P. falciparum CQ-resistant strain W2. Against the promastigote forms of L. donovani, the phenanthrolines 1h, 1j, 1n and 1o were the most active with IC50 from 2.52 to 4.50 μM. The phenanthroline derivative 1o was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 91 on T. brucei brucei strain. FRET melting and native mass spectrometry experiments evidenced that the nitrogen heterocyclic derivatives bind the telomeric G-quadruplexes of P. falciparum and Trypanosoma. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma could be considered to be possible targets of this kind of nitrogen heterocyclic derivatives, their potential ability to stabilize the parasitic telomeric G-quadruplexes have been determined through the FRET melting assay and by native mass spectrometry.

Multicellular development produces patterns of specialized cell types. Yet, it is often unclear how individual cells within a field of identical cells initiate the patterning process. Using live imaging, quantitative image analyses and modeling, we show that during Arabidopsis thaliana sepal development, fluctuations in the concentration of the transcription factor ATML1 pattern a field of identical epidermal cells to differentiate into giant cells interspersed between smaller cells. We find that ATML1 is expressed in all epidermal cells. However, its level fluctuates in each of these cells. If ATML1 levels surpass a threshold during the G2 phase of the cell cycle, the cell will likely enter a state of endoreduplication and become giant. Otherwise, the cell divides. Our results demonstrate a fluctuation-driven patterning mechanism for how cell fate decisions can be initiated through a random yet tightly regulated process.