Neuroanatomical organization of gonadotropin-releasing hormone neurons during the oestrus cycle in the ewe

BACKGROUND: During the preovulatory surge of gonadotropin-releasing hormone (GnRH), a very large amount of the peptide is released in the hypothalamo-hypophyseal portal blood for 24-36H00. To study whether this release is linked to a modification of the morphological organization of the GnRH-containing neurons, i.e. morphological plasticity, we conducted experiments in intact ewes at 4 different times of the oestrous cycle (before the expected LH surge, during the LH surge, and on day 8 and day 15 of the subsequent luteal phase). The cycle stage was verified by determination of progesterone and LH concentrations in the peripheral blood samples collected prior to euthanasia. RESULTS: The distribution of GnRH-containing neurons throughout the preoptic area around the vascular organ of the lamina terminalis was studied following visualisation using immunohistochemistry. No difference was observed in the staining intensity for GnRH between the different groups. Clusters of GnRH-containing neurons (defined as 2 or more neurons being observed in close contact) were more numerous during the late follicular phase (43 ± 7) than during the luteal phase (25 ± 6), and the percentage of clusters was higher during the beginning of the follicular phase than during the luteal phase. There was no difference in the number of labelled neurons in each group. CONCLUSIONS: These results indicate that the morphological organization of the GnRH-containing neurons in ewes is modified during the follicular phase. This transitory re-organization may contribute to the putative synchronization of these neurons during the surge. The molecular signal inducing this plasticity has not yet been identified, but oestradiol might play an important role, since in sheep it is the only signal which initiates the GnRH preovulatory surge

Patello-Femoral Arthroplasty- Indications and Contraindications

: Patellofemoral arthroplasty (PFA) is emerging as an attractive alternative to total knee arthroplasty (TKA) for isolated patellofemoral-osteoarthritis (PF-OA) for selected patients. The success of PFA is highly dependent on patient selection. This intervention is still burdened with a higher rate of revisions and a lower survival rate than TKA when the indications or the surgical technique are not optimal. We highlight the indications and contraindications of PFA to obtain satisfying functional outcomes and survivorship. Preoperative clinical and radiological assessment is critical to determine the presence of PFA indications, the absence of contraindications, and the necessity of any associated procedures, particularly for the tibial tubercle. The typical indications are patients with isolated symptomatic PF-OA, with trochlear dysplasia, when bone-on-bone Iwano 4 osteoarthritis is observed, without significant malalignment, and with the absence of risk factors for developing progressive tibiofemoral-OA. The three main causes of isolated PF-OA are primary OA, trochlear dysplasia, and posttraumatic OA following patellar fracture. Trochlear dysplasia is the preferred indication for PFA. Lack of experience with arthroplasty or realignment of the extensor mechanism is a relative contraindication to performing PFA

La récupération de l état de santé et le stress post-traumatique chez les enfants accidentés de la route (une étude de cohorte)

Cette thèse étudie les facteurs prédictifs et les facteurs associés à la récupération de l état de santé et au stress post-traumatique chez l enfant après un accident de la route. Il s agit d une étude de cohorte prospective mise en place en 2004 composée de 204 enfants de moins de 16 ans, hospitalisés dans les hôpitaux publiques et privés du département du Rhône à la suite d un accident de la route. Un an après l accident, parmi les 127 enfants évalués par questionnaires, 78 (75,0 %) enfants légèrement ou modérément blessés et 8 (34,8%) enfants gravement blessés estimaient avoir complétement récupéré leur état de santé. Après ajustement, le score de gravité (M-AIS>=3) et les lésions des membres inférieurs (AIS>1) étaient associés à la non récupération de l état de santé : Odds Ratio pondérés (ORw) respectifs de 4,3 [IC 95%, 1,3-14,6] et 6,5 [IC 95%, 1,9-21,7]. L état de récupération était significativement corrélé au score physique de la qualité de vie (r=0,46) et dans une moindre mesure au score psychosocial de qualité de vie (r=0,21). D importants symptômes de stress post-traumatique étaient présents chez 26 (27,7%) enfants un an après un accident de la route et cela indépendamment de la gravité des lésions initiales. Dans cette cohorte pédiatrique d accidentés de la route, les enfants ayant des lésions graves (M-AIS>=3) ou des lésions des membres inférieurs avaient une moins bonne récupération de l état de santé à un an. Un état de santé altéré était associé à une qualité de vie plus faible à un an. Il parait important de ne pas négliger les conséquences que peuvent avoir les accidents de la route sur la santé physique et psychique des enfants légèrement blessés.The aim of this thesis was to evaluate predictive factors of recovery and post-traumatic stress in children one year after road traffic injuries. This prospective cohort study was composed of 204 children aged =3) and lower limb injury (AIS>=2) were associated with no full recovery of health status: Weighted Odds Ratio (ORw) : 4.3 [95% Confidence Interval (95% CI) : 1.3-14.6] and ORw : 6.5 [95% CI : 1.9-21.7] respectively. The recovery status was significantly correlated to quality of life Physical scores (r=0.46) especially to Body Pain (r=0.48) and Role/Social physical (r=0.50) and to a lesser extent to quality of life Psychosocial scores (r=0.21). Important post-traumatic stress symptoms were present in 27.7% of children one year after a road traffic accident. In a cohort of children injured in a road accident, those with high injury severity score and those with lower limb injuries are more likely to not fully recover their health status at 1 year. Altered health status was associated with a lower physical quality of life score at 1 year. It seems important to consider psychological consequences road traffic accidents may have on children even after mild or moderate injuries.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Cost-effectiveness of a bone substitute delivering gentamicin in the treatment of chronic osteomyelitis of long bones: Protocol for the CONVICTION randomized multicenter study

IntroductionChronic osteomyelitis is a serious osteoarticular infection that most often occurs in the long bones, responsible for significant morbidity with the risk of fracture and amputation. Despite advances in both antibiotics and surgical treatment, the probability of recurrence of infection remains at around 20%. Cerament-G (BONESUPPORT AB, Sweden) is a synthetic bone substitute that fills the bone void left by surgery, prevents infection and promotes bone regeneration within this space. Cerament-G also provides the local delivery of high doses of gentamicin over several weeks. Two prospective observational studies described a number of infectious recurrences of 4 and 5% after the use of Cerament-G. Although available in France, Cerament-G is currently not reimbursed and its high cost constitutes a barrier to its use. We hypothesize that the use of Cerament-G will lead to fewer costs to the collectivity while improving patient utility and, as an innovative strategy, will be superior to standard of care on recurrence of infection.Methods and analysisThe Conviction Study is a prospective, multicenter, randomized, single blind study conducted in 14 French Reference Centers for Complex Osteoarticular infections. The main objective is to evaluate the cost-effectiveness of using Cerament-G in the treatment of chronic long bone osteomyelitis by comparing this innovative strategy to standard of care. A cost-utility analysis from the collective perspective will be conducted over a 24-month time horizon after the initial surgery. The outcome for the main medico-economic evaluation will be Quality Adjusted Life Years (QALYs).DiscussionThe study is being conducted throughout the CRIOAc network in France, in referral centers for the management of complex infections which will facilitate patient recruitment. This study has several limitations: the investigators have to be trained to handle the device, and it was impossible to blind the surgeon.ConclusionIf the use of Cerament-G is demonstrated to be superior to leaving the dead space empty during surgery for patients with stage III chronic long bone osteomyelitis, its use will be recommended to improve the prognosis of such patients, and this device may eventually qualify for reimbursement through the French Health Insurance scheme.Ethics and disseminationThis protocol received authorization from the Ethics Committee CPP Sud Méditerranée V on April 27, 2021 (21.03.10.77652) and the French National Agency for Medicines and Health Products on May 6, 2021 (2020-A02299-30). Results will be disseminated to the scientific community through congresses and publication in peer-reviewed journals

2.5D Representations Combining in vivo 3D MRI and ex vivo 2D MSI Approaches to Study the Lipid Distribution in the Whole Sheep Brain

National audienceMass Spectrometry Imaging (MSI) provides easily high spatially resolved masses allowing characterization of endogenous lipids. These latter constitute about 70% of the composition of the white matter of the brain which can be implicated in developmental and/or cognitive troubles. In order to examine the molecular distribution of lipids in whole sheep brain, and especially in white/grey matter, we combined in vivo and ex vivo images, obtained in the same animals, using Magnetic Resonance Imaging (MRI) and MSI, respectively. In order to view the topology of the molecular species within the organ, we propose the construction of a 2.5 D representation where a single section imaged with 2D MSI is localized within the tissue volume obtained by 3D MRI. 3D T1-weighted MPRAGE images were acquired on two anesthetized sheep with a 3 Tesla MRI (Siemens, Verio ®). The parameters of acquisition for the MPRAGE were: TR 2500ms, TE 3.2ms, FA 12, NEX 1, matrix 384×384, FOV 192mm, 288 slices with a thickness of 0.5mm. In order to improve data quality, the 3D MRI volumes have been pre-processed using in-house algorithms using volume fitting and Markov random field methods. T1 3D planes corresponding to MSI planes were reconstructed using Osirix imaging software.Brains were collected after sacrifice and frozen at -80°C. Frontal and sagittal 14 µm brain sections were performed with a cryostat adapted to large sections (CM3050 S, Leica) and mounted onto conductive ITO-coated slides. The spray of α-cyano-4-hydroxycinnamic acid matrix was performed using an Image Prep device (Bruker). Spectra were acquired using an UltrafleXtrem MALDI-TOF instrument (Bruker) in the 200–1200 m/z range with a spatial resolution set at 125 µm. Raw spectra were analyzed with SCiLS Lab software to generate 2D ion density maps and segmentation maps (data partitioning). The tissue sections analyzed by MSI were stained with cresyl violet to manually delimitate neuronal nuclei and areas. This histological map was used to delineate the MRI and MSI 2D views and overlay them regardless the same brain areas used as fiducials. After, a 2.5 D representation was proposed to visualize the lipid distribution within the entire organ.In conclusion, in this study, frontal and sagittal whole sheep brain sections analyzed by MSI showed a clear difference in lipid distribution between different compartments of brain tissues, especially between grey and white matter, until the cerebral envelopment presenting circumvolution. Furthermore, the alignment of 2D MALDI-imaging with T1-weighted images showed that MSI can provide finer details on the structural connectivity of myelinated fiber tracts. Here, the 2.5 D representation combining MRI and MSI was presented as an alternative approach to 3D anatomical and molecular atlas providing a perfect topology of the molecular species within an organ. For the moment, 3D MSI of whole sheep brain is a challenge, while the 2.5 D construction demonstrated to be a capable tool for exploring molecular distributions throughout sample volumes.Nowadays, the reported results may serve as a starting point for further experiments associating MSI and dynamic and functional MRI, especially for the characterization of brain

Time to benefit of heart rate reduction with ivabradine in patients with heart failure and reduced ejection fraction

Aims In the SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial, ISRCTN70429960) study, ivabradine reduced cardiovascular death or heart failure (HF) hospitalizations in patients with HF and reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate (HR) ≥70 bpm. In this study, we sought to determine the clinical significance of the time durations of HR reduction and the significant treatment effect on outcomes among patients with HFrEF. Methods and results The time to statistically significant reduction of the primary outcome (HF hospitalization and cardiovascular death) and its components, all-cause death, and HF death, were assessed in a post-hoc analysis of the SHIFT trial in the overall population (HR ≥70 bpm) and at HR ≥75 bpm, representing the approved label in many countries. Compared to placebo, the primary outcome and HF hospitalizations were significantly reduced at 102 days, while there was no effect on cardiovascular death, all-cause death, and HF death at HR ≥70 bpm. In the population with a baseline HR ≥75 bpm, a reduction of the primary outcome occurred after 67 days, HF hospitalization after 78 days, cardiovascular death after 169 days, death from HF after 157 days and all-cause death after 169 days. Conclusion Treatment with ivabradine should not be deferred in patients in sinus rhythm with a HR of ≥70 bpm to reduce the primary outcome and HF hospitalizations, in particular in patients with HR ≥75 bpm. At HR ≥75 bpm, the time to risk reduction was shorter for reduction of hospitalization and mortality outcomes in patients with HFrEF after initiation of guideline-directed medication, including beta-blockers at maximally tolerated doses

New measurement technique for restoration of the trochlear offset after image-based robotic-assisted total knee arthroplasty: a reliability study

Introduction: The new concepts in total knee arthroplasty (TKA) tend to improve the alignment and ligament balancing after TKA. Nevertheless, the assessment of the anterior compartment is difficult. The purpose of this study was to describe a new measurement technique of trochlear offset restoration on CT-scan after primary robotic-assisted TKA and assess its reliability and repeatability. Method: This monocentric study assessed the trochlear offset restoration on a CT scan after 20 robotic-assisted TKA. To evaluate the trochlear offset restoration, we measured the depth difference between the native and the prosthetic trochlea. Four sequential positions were assessed on the trochlea: at full extension, at 30°, 70°, and 90° flexion. For each of these positions, we compared the highest point of the lateral native condyle and the lateral prosthetic condyle, the highest point of the medial native condyle and the medial prosthetic condyle, the deepest point of the native trochlear groove and the prosthetic trochlea. Two independent reviewers performed the measurements to assess their reliability. To determine intraobserver variability, the first observer performed the measurements twice. Results: The mean age was 67.3 years old ± 8.3. Mean values of the trochlear offset restoration for the medial condyle, trochlear groove and lateral condyle were respectively: 1.0 mm ± 1.6, 1.1 mm ± 1.5, −2.7 mm ± 2.3 in full extension; −3.5 mm ± 1.7, −1.5 mm ± 1.7, −3.9 mm ± 3.9 at 30° flexion; −5.1 mm ± 1.8, 2.1 mm ± 2.7, −3.8 mm ± 1.8 at 70° flexion; 2.0 mm ± 1.4 and 3.1 mm ± 1.5 for the medial and lateral condyles at 90° flexion. The radiographic measurements showed very good to excellent intra-observer and inter-observer agreements with mean kappa values of 0.92 and 0.74. Conclusion: We present a novel measurement technique on CT scan for evaluating the restoration of the trochlear offset after TKA, demonstrating excellent inter and intra-observer reliability

A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

YesAnimals have evolved diverse seasonal variations in physiology and reproduction to accommodate yearly changes in environmental and climatic conditions. These changes in physiology are initiated by changes in photoperiod (daylength) and are mediated through melatonin, which relays photoperiodic information to the pars tuberalis of the pituitary gland. Melatonin drives thyroid‐stimulating hormone transcription and synthesis in the pars tuberalis, which, in turn, regulates thyroid hormone and retinoic acid synthesis in the tanycytes lining the third ventricle of the hypothalamus. Seasonal variation in central thyroid hormone signalling is conserved among photoperiodic animals. Despite this, different species adopt divergent phenotypes to cope with the same seasonal changes. A common response amongst different species is increased hypothalamic cell proliferation/neurogenesis in short photoperiod. That cell proliferation/neurogenesis may be important for seasonal timing is based on (i) the neurogenic potential of tanycytes; (ii) the fact that they are the locus of striking seasonal morphological changes; and (iii) the similarities to mechanisms involved in de novo neurogenesis of energy balance neurones. We propose that a decrease in hypothalamic thyroid hormone and retinoic acid signalling initiates localised neurodegeneration and apoptosis, which leads to a reduction in appetite and body weight. Neurodegeneration induces compensatory cell proliferation from the neurogenic niche in tanycytes and new cells are born under short photoperiod. Because these cells have the potential to differentiate into a number of different neuronal phenotypes, this could provide a mechanistic basis to explain the seasonal regulation of energy balance, as well as reproduction. This cycle can be achieved without changes in thyroid hormone/retinoic acid and explains recent data obtained from seasonal animals held in natural conditions. However, thyroid/retinoic acid signalling is required to synchronise the cycles of apoptosis, proliferation and differentiation. Thus, hypothalamic neurogenesis provides a framework to explain diverse photoperiodic responses.MRC. Grant Number: MR/P012205/1 - Scottish Government - BBSRC. Grant Number: BB/K001043/1 - Physiological Societ

Efficacy of ivabradine in heart failure patients with a high-risk profile (analysis from the SHIFT trial)

Aims Early start and patient profile-oriented heart failure (HF) management has been recommended. In this post hoc analysis from the SHIFT trial, we analysed the treatment effects of ivabradine in HF patients with systolic blood pressure (SBP) < 110 mmHg, resting heart rate (RHR) ≥ 75 b.p.m., left ventricular ejection fraction (LVEF) ≤ 25%, New York Heart Association (NYHA) Class III/IV, and their combination. Methods and results The SHIFT trial enrolled 6505 patients (LVEF ≤ 35% and RHR ≥ 70 b.p.m.), randomized to ivabradine or placebo on the background of guideline-defined standard care. Compared with placebo, ivabradine was associated with a similar relative risk reduction of the primary endpoint (cardiovascular death or HF hospitalization) in patients with SBP < 110 and ≥110 mmHg [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.74–1.08 vs. HR 0.80, 95% CI 0.72–0.89, P interaction = 0.34], LVEF ≤ 25% and >25% (HR 0.85, 95% CI 0.72–1.01 vs. HR 0.80, 95% CI 0.71–0.90, P interaction = 0.53), and NYHA III–IV and II (HR 0.83, 95% CI 0.74–0.94 vs. HR 0.81, 95% CI 0.69–0.94, P interaction = 0.79). The effect was more pronounced in patients with RHR ≥ 75 compared with <75 (HR 0.76, 95% CI 0.68–0.85 vs. HR 0.97, 95% CI 0.81–0.1.16, P interaction = 0.02). When combining these profiling parameters, treatment with ivabradine was also associated with risk reductions comparable with patients with low-risk profiles for the primary endpoint (relative risk reduction 29%), cardiovascular death (11%), HF death (49%), and HF hospitalization (38%; all P values for interaction: 0.40). No safety concerns were observed between study groups. Conclusions Our analysis shows that RHR reduction with ivabradine is effective and improves clinical outcomes in HF patients across various risk indicators such as low SBP, high RHR, low LVEF, and high NYHA class to a similar extent and without safety concern

Contributions of the anterolateral complex and the anterolateral ligament to rotatory knee stability in the setting of ACL Injury: a roundtable discussion

© 2017, European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA). Persistent rotatory knee laxity is increasingly recognized as a common finding after anterior cruciate ligament (ACL) reconstruction. While the reasons behind rotator knee laxity are multifactorial, the impact of the anterolateral knee structures is significant. As such, substantial focus has been directed toward better understanding these structures, including their anatomy, biomechanics, in vivo function, injury patterns, and the ideal procedures with which to address any rotatory knee laxity that results from damage to these structures. However, the complexity of lateral knee anatomy, varying dissection techniques, differing specimen preparation methods, inconsistent sectioning techniques in biomechanical studies, and confusing terminology have led to discrepancies in published studies on the topic. Furthermore, anatomical and functional descriptions have varied widely. As such, we have assembled a panel of expert surgeons and scientists to discuss the roles of the anterolateral structures in rotatory knee laxity, the healing potential of these structures, the most appropriate procedures to address rotatory knee laxity, and the indications for these procedures. In this round table discussion, KSSTA Editor-in-Chief Professor Jón Karlsson poses a variety of relevant and timely questions, and experts from around the world provide answers based on their personal experiences, scientific study, and interpretations of the literature. Level of evidence V