Patient-Specific Surgical Correction of Adolescent Idiopathic Scoliosis: A Systematic Review

The restoration of sagittal alignment is fundamental to the surgical correction of adolescent idiopathic scoliosis (AIS). Despite established techniques, some patients present with inadequate postoperative thoracic kyphosis (TK), which may increase the risk of proximal junctional kyphosis (PJK) and imbalance. There is a lack of knowledge concerning the effectiveness of patient-specific rods (PSR) with measured sagittal curves in achieving a TK similar to that planned in AIS surgery, the factors influencing this congruence, and the incidence of PJK after PSR use. This is a systematic review of all types of studies reporting on the PSR surgical correction of AIS, including research articles, proceedings, and gray literature between 2013 and December 2023. From the 28,459 titles identified in the literature search, 81 were assessed for full-text reading, and 7 studies were selected. These included six cohort studies and a comparative study versus standard rods, six monocentric and one multicentric, three prospective and four retrospective studies, all with a scientific evidence level of 4 or 3. They reported a combined total of 355 AIS patients treated with PSR. The minimum follow-up was between 4 and 24 months. These studies all reported a good match between predicted and achieved TK, with the main difference ranging from 0 to 5 degrees, p > 0.05, despite the variability in surgical techniques and the rods' properties. There was no proximal junctional kyphosis, whereas the current rate from the literature is between 15 and 46% with standard rods. There are no specific complications related to PSR. The exact role of the type of implants is still unknown. The preliminary results are, therefore, encouraging and support the use of PSR in AIS surgery

Enhanced recovery following posterior spinal fusion for adolescent idiopathic scoliosis: A medical and economic study in a French private nonprofit pediatric hospital

Introduction: Little data exist on the efficacy of enhanced recovery after surgery (ERAS) protocols in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Hypothesis: ERAS reduces hospital costs (HC) and length of stay (LOS) without increasing pain or complications. Materials and methods: This was a retrospective comparative medical and economic study of 2 cohorts of patients who underwent PSF for AIS: a prospective group who underwent surgery with an ERAS protocol without a specially assigned care coordinator from 2020 to 2021 (n=30) and a retrospective group (control) who received standard care from 2017 to 2018 (n=30). The key amendments to the ERAS protocol were reduced preoperative investigations, opioid-sparing analgesia, ambulation starting on postoperative day (POD) 1, early resumption of oral diet, and early transition to oral analgesics. Moreover, an intensive care unit (ICU) stay, surgical drainage, and the postoperative CT scan were no longer routine. The discharge criteria were the same for both groups: normal bowel function, independent walking, pain Visual Analog Scale (VAS)<3 without strong opioids, and no signs of complications. The endpoints were: decreased HC (calculated by subtracting the costs of hospital days and complementary exams that were not carried out) and LOS, complications, and postoperative pain according to the VAS on POD 1, POD 3, and discharge. All means were reported with the standard deviation. Results: The mean age of patients undergoing surgery (14.5±1.7 years), sex ratio, curve type according to the Lenke classification, mean Cobb angle (54±12°), and the number of instrumented vertebrae (9±2) were similar in both groups (p>0.5). The HC decreased on average by 3029€ per patient. The mean LOS was 5±0.9 days in the ERAS group versus 6.5±0.6 days in the control group (p<0.001). The VAS scores on POD 1 and POD 3 were lower in the ERAS group. One postoperative complication was noted in each group. Conclusion: Implementing an ERAS protocol without a specifically assigned care coordinator for patients with AIS undergoing PSF significantly decreased HC, LOS, and early postoperative pain. Level of evidence: III; retrospective comparative study

Assessment of sediment and organic carbon exports into the Arctic ocean: the case of the Yenisei river basin

The export of organic carbon export by the rivers to the oceans either as particulate organic carbon (POC) or dissolved organic carbon (DOC) is very sensitive to climate change especially in permafrost affected catchments where soils are very rich in organic carbon. With global warming, organic carbon export in both forms is expected to increase in Arctic regions. It should affect contemporary biogeochemical cycles in rivers and oceans and therefore modify the whole food web. This study tries to understand complex processes involved in sediment, POC and DOC riverine transport in the Yenisei River basin and to quantify their respective fluxes at the river outlet. The SWAT (Soil and Water Assessment Tool) hydrological model is used in this study to simulate water and suspended sediment transfers in the largest Arctic river. POC and DOC export have been quantified with empirical models, adapted from literature for the study case. First, the hydrological model has been calibrated and validated at a daily time step for the 2003–2008 and the 2009–2016 periods respectively, and its output has been compared with field data for water and sediment fluxes. Based on conceptualization of transfer processes, calibration on climate and soil properties has been performed in order to correctly represent hydrology and sediment transfer in permafrost basins. Second, calibration of empirical models for DOC/POC transport have been performed by comparing their output with field data, available from 2003 to 2016. Our study reveals that SWAT is capable of correctly representing hydrology, sediment transfer, POC and DOC fluxes and their spatial distribution at a daily timescale, and outlines the links between these fluxes and permafrost features. Our simulation effort results in specific sediment, POC and DOC fluxes of 2.97 t km−2 yr−1, 0.13 t km−2 yr−1 and 1.14 t km−2 yr−1 for the period 2003–2016 which are in the range of previous estimates. About 60% of the total fluxes of sediment, DOC and POC to the Arctic Ocean are exported during the two months of the freshet. Spatial analysis show that permafrost-free areas have returned higher daily organic carbon export than permafrost affected zones, highlighting the thawing permafrost effect on carbon cycle in climate change feedback

La détection des sites de la Préhistoire ancienne en Hauts-de-France

National audienc

La détection des sites de la Préhistoire ancienne en Hauts-de-France

National audienc

La détection des sites de la Préhistoire ancienne en Hauts-de-France

National audienc

Rationally Designed Cu(I) Ligand to Prevent CuAβ-Generated ROS Production in the Alzheimer’s Disease Context

In the context of Alzheimer’s disease, copper (Cu) can be loosely bound to the amyloid-β (Aβ) peptide, leading to the formation of CuAβ, which can catalytically generate reactive oxygen species that contribute to oxidative stress. To fight against this phenomenon, the chelation therapy approach has been developed and consists of using a ligand able to remove Cu from Aβ and to redox-silence it, thus stopping the reactive oxygen species (ROS) production. A large number of Cu(II) chelators has been studied, allowing us to define and refine the properties required to design a “good” ligand, but without strong therapeutic outcomes to date. Those chelators targeted the Cu(II) redox state. Herein, we explore a parallel and relevant alternative pathway by designing a chelator able to target the Cu(I) redox state. To that end, we designed LH2 ([1N3S] binding set) and demonstrated that (i) it is perfectly able to extract Cu(I) from Cu(I)Aβ even in the presence of an excess of Zn(II) and (ii) it redox-silences the Cu, preventing the formation of ROS. We showed that LH2 that is sensitive to oxidation can efficiently replace the [Zn(II)L] complex without losing its excellent ability to stop the ROS production while increasing its resistance to oxidation

Multimetallic Zirconocene-Based Catalysis: Alkyne Dimerization and Cyclotrimerization Reactions

International audienceSystematic exploration of zirconocene (Cp2ZrII) chemistry since the 1980s has offered a wide range of useful methods for organic synthesis. Many of these reactions are stoichiometric in zirconium, and even if several catalytic reactions are known, the development of catalytic zirconocene chemistry is of continuing interest. In this paper, the study of reactions catalytic in zirconium, i.e. alkyne dimerization and cyclotrimerization, is presented. These reactions are carried out by employing the recently introduced lanthanide-originated zirconocene equivalent. The use of 10 mol % of Cp2ZrCl2, together with La metal or mischmetall as reductant and AlCl3 as transmetalating agent, leads to an efficient formation of dienes from disubstituted alkynes. Under the same conditions, monosubstituted alkynes underwent cyclotrimerization reactions to afford benzene derivatives. This reaction also occurs efficiently in the absence of AlCl3. It was postulated that the catalytic cyclotrimerization did not proceed through a typical insertion of the alkyne into the zirconacyclopentadiene intermediate. This unprecedented reaction takes place in the presence of zirconocene and lanthanide species, possibly involving a bimetallic polarization process

Ring Substituents Mediate the Morphology of PBDTTPD-PCBM Bulk-Heterojunction Solar Cells

Among π-conjugated polymer donors for efficient bulk-heterojunction (BHJ) solar cell applications, poly­(benzo­[1,2-<i>b</i>:4,5-<i>b</i>′]­dithiophene–thieno­[3,4-<i>c</i>]­pyrrole-4,6-dione) (PBDTTPD) polymers yield some of the highest open-circuit voltages (V_OC, ca. 0.9 V) and fill-factors (FF, ca. 70%) in conventional (single-cell) BHJ devices with PCBM acceptors. In PBDTTPD, side chains of varying size and branching affect polymer self-assembly, nanostructural order, and impact material performance. However, the role of the polymer side-chain pattern in the intimate mixing between polymer donors and PCBM acceptors, and on the development of the BHJ morphology is in general less understood. In this contribution, we show that ring substituents such as furan (F), thiophene (T) and selenophene (S)incorporated into the side chains of PBDTTPD polymerscan induce significant and, of importance, very different morphological effects in BHJs with PCBM. A combination of experimental and theoretical (via density functional theory) characterizations sheds light on how varying the heteroatom of the ring substituents impacts (i) the preferred side-chain configurations and (ii) the ionization, electronic, and optical properties of the PBDTTPD polymers. In parallel, we find that the PBDT­(X)­TPD analogs (with <i>X</i> = F, T, or S) span a broad range of power conversion efficiencies (PCEs, 3–6.5%) in optimized devices with improved thin-film morphologies via the use of 1,8-diiodooctane (DIO), and discuss that persistent morphological impediments at the nanoscale can be at the origin of the spread in PCE across optimized PBDT­(X)­TPD-based devices. With their high <i>V</i>_OC ∼1 V, PBDT­(X)­TPD polymers are promising candidates for use in the high-band gap cell of tandem solar cells

Discovery of (2<i>S</i>)‑8-[(3<i>R</i>)‑3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro‑2<i>H</i>‑pyrimido[1,2‑<i>a</i>]pyrimidin-6-one: A Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors

Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimido­pyrimidinone derivatives. Starting with hit compound <b>1a</b>, medicinal chemistry optimization led to compound <b>31</b>. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound <b>31</b> in human Vps34 illustrates how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound <b>31</b> constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology