Granulosa cells provide elimination of apoptotic oocytes through unconventional autophagy-assisted phagocytosis.

STUDY QUESTION: Do human granulosa cells (GCs) ingest and destroy apoptotic oocytes? SUMMARY ANSWER: Somatic GCs ingest and destroy apoptotic oocytes and other apoptotic substrates through unconventional autophagy-assisted phagocytosis. WHAT IS KNOWN ALREADY: Most (99%) ovarian germ cells undergo apoptosis through follicular atresia. The mode of cleaning of atretic follicles from the ovary is unclear. Ovarian GCs share striking similarities with testicular Sertoli cells with respect to their origin and function. Somatic Sertoli cells are responsible for the elimination of apoptotic spermatogenic cells through unconventional autophagy-assisted phagocytosis. STUDY DESIGN, SIZE, DURATION: Human GCs were tested for the ability to ingest and destroy the apoptotic oocytes and other apoptotic substrates. A systemic study of the main phagocytosis steps has been performed at different time points after loading of apoptotic substrates into the GC. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary cultures of GC retrieved following controlled ovarian stimulation of five women for IVF/ICSI and a human granulosa KGN cell line were incubated with different apoptotic substrates: oocytes which underwent spontaneous apoptosis during the cultivation of immature germ cells for IVF/ICSI; apoptotic KGN cells; and apoptotic membranes from rat retinas. Cultured GC were analyzed for the presence of specific molecular markers characteristic of different steps of phagocytic and autophagy machineries by immunocytochemistry, confocal microscopy, transmission electron microscopy and western blotting, before and after loading with apoptotic substrates. MAIN RESULTS AND THE ROLE OF CHANCE: Incubation of human GC with apoptotic substrates resulted in their translocation in cell cytoplasm, concomitant with activation of the phagocytosis receptor c-mer proto-oncogene tyrosine kinase MERTK (P < 0.001), clumping of motor molecule myosin II, recruitment of autophagy proteins: autophagy-related protein 5 (ATG5), autophagy-related protein 6 (Beclin1) and the rise of a membrane form of microtubule-associated protein 1 light chain 3 (LC3-II) protein. Ingestion of apoptotic substrates was accompanied by increased expression of the lysosomal protease Cathepsin D (P < 0.001), and a rise of lysosomes in the GCs, as assessed by different techniques. The level of autophagy adaptor, sequestosome 1/p62 (p62) protein remained unchanged. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The number of patients described here is limited. Also the dependence of phagocytosis on reproductive hormone status of patients should be analyzed. WIDER IMPLICATIONS OF THE FINDINGS: Removal of apoptotic oocytes by surrounding GC seems likely to be a physiological mechanism involved in follicular atresia. Proper functioning of this mechanism may be a new strategy for the treatment of ovarian dysfunctions associated with an imbalance in content of germ cells in the ovaries, such as premature ovarian failure and polycystic ovary syndrome. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Rennes Metropole (AIS 2015) and Agence de BioMédecine. This work was supported by funding from Université de Rennes1, Institut National de la Santé et de la Recherche Médicale (INSERM) and CHU de Rennes. A.B. is funded in part by the program Actions Concertées Interpasteuriennes (ACIP) and a research grant from the European Society of Pediatric Endocrinology. This work is supported by the Agence Nationale de la Recherche Grants ANR-17-CE14-0038 and ANR-10-LABX-73. The authors declare no competing interests.

[Enhanced recovery after surgery in colorectal surgery]. / La réhabilitation améliorée après chirurgie colorectale.

Enhanced recovery after surgery (ERAS) in colorectal surgery consists of multidisciplinary, multimodal, and patient-centred care. The implementation of pre-, intra-, and post-operative measures mitigates the surgical stress, the inflammatory reaction, and their consequences. The elements of this protocol are evidence-based medicine. This allows improved and accelerated recovery. Consequently, ERAS reduces the incidence of medical complications by 50 %, including fewer infectious complications, and a possible positive impact on survival after oncologic surgery. Hospital length of stay is shortened. There is no contraindication to ERAS, which must be used for all patients undergoing colorectal surgery. Adaptation of the protocol will nevertheless be necessary in the event of urgent surgery.

La réhabilitation améliorée après chirurgie (RAC) colorectale est une prise en charge multidisciplinaire et multimodale, centrée sur le patient. La mise en place de mesures pré-, per- et postopératoires réduit la réponse au stress chirurgical, la réaction inflammatoire et leurs conséquences. Ce protocole de soins, basé sur des preuves scientifiques, permet une récupération améliorée et accélérée. L'incidence des complications médicales est, secondairement, réduite de 50 %. La réhabilitation améliorée se traduit par une diminution significative de la durée d'hospitalisation, une diminution des complications infectieuses et, probablement, par un impact positif sur la survie après chirurgie oncologique. Il n'y a pas de contre-indication à la RAC qui doit donc être proposée à tous les patients devant subir une chirurgie colorectale. Une adaptation du protocole sera néanmoins nécessaire en cas de chirurgie urgente.

Identification of suitable endogenous controls for gene and miRNA expression studies in irradiated prostate cancer cells.

This study aimed to to evaluate the stability of commonly used endogenous control genes for messenger RNA (mRNA) (N = 16) and miRNAs (N = 3) expression studies in prostate cell lines following irradiation. The stability of endogenous control genes expression in irradiated (6 Gy) versus unirradiated controls was quantified using NormFinder and coefficient of variation analyses. HPRT1 and 18S were identified as most and least stable endogenous controls, respectively, for mRNA expression studies in irradiated prostate cells. SNORD48 and miR16 miRNA endogenous controls tested were associated with low coefficient of variations following irradiation (6 Gy). This study highlights that commonly used endogenous controls can be responsive to radiation and validation is required prior to gene/miRNAs expression studies.

Ambient hypoxia enhances the loss of muscle mass after extensive injury.

Hypoxia induces a loss of skeletal muscle mass and alters myogenesis in vitro, but whether it affects muscle regeneration in vivo following injury remains to be elucidated. We hypothesized that hypoxia would impair the recovery of muscle mass during regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14, and 28 days under normoxia or hypobaric hypoxia (5,500 m) conditions. Hypoxia impaired the formation and growth of new myofibers and enhanced the loss of muscle mass during the first 7 days of regeneration, but did not affect the final recovery of muscle mass at 28 days. The impaired regeneration under hypoxic conditions was associated with a blunted activation of mechanical target of rapamycin (mTOR) signaling as assessed by p70(S6K) and 4E-BP1 phosphorylation that was independent of Akt activation. The decrease in mTOR activity with hypoxia was consistent with the increase in AMP-activated protein kinase activity, but not related to the change in regulated in development and DNA response 1 protein content. Hypoxia increased the mRNA levels of the atrogene muscle ring finger-1 after 7 days of regeneration, though muscle atrophy F box transcript levels remained unchanged. The increase in MyoD and myogenin mRNA expression with regeneration was attenuated at 7 days with hypoxia. In conclusion, our results support the notion that the enhanced loss of muscle mass observed after 1 week of regeneration under hypoxic conditions could mainly result from the impaired formation and growth of new fibers resulting from a reduction in protein synthesis and satellite cell activity.

Knee arthroscopic surgery is beneficial to middle-aged patients with meniscal symptoms: a prospective, randomised, single-blinded study.

OBJECTIVE: There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments. This randomised controlled trial aimed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy. METHOD: 150 out of 179 eligible patients, aged 45 to 64 (mean:54 ± 5), symptom duration more than 3 months and standing X-ray with Ahlbäck grade 0, were randomised to: (1) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme (non-surgery group); or (2) the same as (1) plus, within 4 weeks of inclusion, knee arthroscopy for resection of any significant meniscal injuries (surgery group). The primary outcome was change in pain at 12 months, assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOSPAIN). RESULTS: In the Intention-To-Treat analysis, pain at 12 months was significantly lower in the surgery than in the non-surgery group. The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group (between-group difference was 10.6 points of change; 95% CI: 3.4 to 17.7, P = 0.004). The As-Treated analysis results were consistent with the Intention-To-Treat analysis results. CONCLUSION: Middle-aged patients with meniscal symptoms may benefit from arthroscopic surgery in addition to a structured exercise programme. Patients' age or symptom history (i.e., mechanical symptoms or acute onset of symptoms) didn't affect the outcome. TRIAL REGISTRATION: NCT01288768.

Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration.

Hypoxia impairs the muscle fibre-type shift from fast-to-slow during post-natal development; however, this adaptation could be a consequence of the reduced voluntary physical activity associated with hypoxia exposure rather than the result of hypoxia per se. Moreover, muscle oxidative capacity could be reduced in hypoxia, particularly when hypoxia is combined with additional stress. Here, we used a model of muscle regeneration to mimic the fast-to-slow fibre-type conversion observed during post-natal development. We hypothesised that hypoxia would impair the recovery of the myosin heavy chain (MHC) profile and oxidative capacity during muscle regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14 and 28 days under normoxia or hypobaric hypoxia (5,500 m altitude) conditions. Ambient hypoxia did not impair the recovery of the slow MHC profile during muscle regeneration. However, hypoxia moderately decreased the oxidative capacity (assessed from the activity of citrate synthase) of intact muscle and delayed its recovery in regenerated muscle. Hypoxia transiently increased in both regenerated and intact muscles the content of phosphorylated AMPK and Pgc-1α mRNA, two regulators involved in mitochondrial biogenesis, while it transiently increased in intact muscle the mRNA level of the mitophagic factor BNIP3. In conclusion, hypoxia does not act to impair the fast-to-slow MHC isoform transition during regeneration. Hypoxia alters the oxidative capacity of intact muscle and delays its recovery in regenerated muscle; however, this adaptation to hypoxia was independent of the studied regulators of mitochondrial turn-over.

Surgical management of dysthyroid optic neuropathy: A systematic review.

OBJECTIVE: There is currently no recommendation on the optimal surgical management for dysthyroid optic neuropathy (DON). The aim of this study is to systematically review the surgical management of DON and its outcome on visual acuity (VA). DATA SOURCES: MEDLINE, Cochrane Library, and clinicaltrials.gov REVIEW METHODS: A systematic review of studies about the surgical management of DON was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles were included if preoperative and postoperative VA in logMAR (Logarithm of the Minimum Angle of Resolution) were available. RESULTS: Fifteen articles were included in the study accounting for 669 orbits. The mean VA improvement was of 0.44 logMAR overall, 0.41 logMAR for 1-wall, 0.41 logMAR for 2-wall, and 0.55 logMAR for 3-wall decompressions. The mean reduction in exophthalmos was 4.9 mm overall, 4.3 mm for 1-wall, 4.54 mm for 2-wall, and 6.02 for 3-wall decompressions. The mean new onset diplopia (NOD) rate was 19.84% overall, 19,12% for 1-wall, 20.75% for 2-wall, and 19.83% for 3-wall decompressions. CONCLUSION: The results are limited due to the high number of biases in the included studies. It seems that 3-wall decompression offers the best VA improvement and proptosis reduction although also the highest NOD and complications rate. Two-wall balanced decompression or 1-wall inferomedial decompression seems to be effective with less morbidity.

Drug-induced uveitis in aids patients: two case reports.

Patients with acquired immunodeficiency syndrome (AIDS) can develop severe uveitis. Although infectious and autoimmune causes must always be considered, drug induced uveitis is also an important etiology. Herein, we present two case reports illustrating the classical presentation of rifabutin and cidofovir induced uveitis. The first case was a 33 year old woman with AIDS treated with anti-protease and anti-tuberculosis drugs (including rifabutin). She presented with a red painful right eye. There was a strong anterior segment inflammation with fibrinous exudates and a dense vitritis. Rifabutin was stopped and topical steroids and mydriatics were given. Intraocular inflammation and symptoms rapidly resolved. The second patient was a 36 year old woman who presented with a painful decrease of vision in her left eye. She was followed for bilateral CMV retinitis in the setting of AIDS and had recently received 2 systemic injections of cidofovir. Anterior segment inflammation with posterior synechiae in both eyes and folds of Descemet membrane in the left eye were noted. Intraocular pressure was 0 mmHg in the left eye and 10 mmHg in the right eye. Fundus examination disclosed CMV retinitis scars in the right eye and choroidal folds in the macula of the left eye. Cidofovir was discontinued and topical steroids and mydriatics started. Progressively the inflammation decreased and the intraocular pressure returned to normal levels. In conclusion, rifabutin and cidofovir are classical examples of drug induced uveitis with distinct characteristic clinical presentation. Recognition of those entities in AIDS patients can avoid useless and potentially invasive interventions in those fragile people.

Bilateral total deafness after preparation of wild boar meat.

INTRODUCTION: Streptococcus suis is responsible for a zoonosis for which Suidae (pigs and wild boars) constitute the reservoir, mainly in Asia, with a much lower prevalence in Europe. The predominant clinical manifestation is meningitis, possibly resulting in deafness. CASE REPORT: We report the case of a woman hospitalised for meningitis complicated by labyrinthitis, occurring several hours after preparing a meal composed of wild boar meat. Despite the presence of intracochlear fibrosis, the patient was managed by sequential bilateral cochlear implants. DISCUSSION: The discussion presents a review of the international literature and describes the mechanisms responsible for hearing loss related to this rare zoonosis.

A sudden bilateral hearing loss caused by inner ear hemorrhage.

INTRODUCTION: Labyrinthine hemorrhage is a rare cause of sudden deafness and generally concerns only on one side. CASE SUMMARY: An 84-year-old man with a past medical history of myelomonocytic chronic leukemia (CMML) suffered from sudden bilateral hearing loss associated with vertigo. The audiogram revealed a left cophosis and a right profound deafness. Videonystagmography showed a left vestibular deficit. The MRI showed a spontaneous strong T1 weighted signal in the left and right labyrinths, corresponding to a bilateral inner ear hemorrhage (IEH). Dizziness resolved rapidly following vestibular physiotherapy, in contrast to hearing which did not improve at all and let the patient isolated in his environment. The patient successfully underwent cochlear implantation so that he could communicate. DISCUSSION: Most IEHs are unilateral and due to anticoagulants treatments and hematological diseases. Only rare cases have described bilateral labyrinth hemorrhage. This is the first case reported of bilateral labyrinth hemorrhage due to CMML.

Comparison of pulsed-field gel electrophoresis and whole-genome-sequencing-based typing confirms the accuracy of pulsed-field gel electrophoresis for the investigation of local Pseudomonas aeruginosa outbreaks.

AIM: To determine whether pulsed-field gel electrophoresis (PFGE) accurately recognizes isolates belonging to clusters defined by techniques based on whole-genome sequencing (WGS) using Pseudomonas aeruginosa as a model. METHODS: We selected 65 isolates of ST395 P. aeruginosa isolated in seven European hospitals between 1998 and 2012. Isolates were typed by PFGE and sequenced by WGS. A core genome multi-locus sequence typing (cgMLST) analysis based on 3831 genes was performed with a homemade pipeline. FINDINGS: PFGE identified eight pulsotypes and cgMLST differentiated nine clusters and nine singletons. Five cgMLST clusters and pulsotypes (31/65 isolates) coincided perfectly. Isolates without evident epidemiological links grouped by PFGE were separated by cgMLST (16/65 isolates) differentiating cities, suggesting that PFGE should be kept for the investigation of local outbreaks. Importantly, hypermutator isolates still shared the pulsotype with their parents (16/65 isolates), whereas they were not recognized by cgMLST. This shows that PFGE was less affected than WGS-based typing by the accelerated genetic drift that occurs in epidemic P. aeruginosa. CONCLUSIONS: although WGS-based typing has logically become the new reference standard, we show here that the PFGE can be used with confidence for the investigation of local outbreaks caused by P. aeruginosa.

Lentiviral vectors for gene transfer into the spinal cord glial cells.

Activated glial cells in the dorsal spinal cord participate in the development and maintenance of pain after peripheral nerve injury. Our understanding of mechanisms involved in functional changes of spinal glia remains incomplete. Excepting drugs that completely disrupt glial function, pharmacological studies fail to target glia and to modify locally its function to really discriminate the function of neuronal versus glial cells in chronic pain. Lentivirus-derived vectors fulfill several criteria that make them potentially interesting for this preferential targeting of glial cells in the spinal cord. We showed that in vivo single microdelivery of vesicular stomatitis virus G pseudotyped lentiviral vectors into the rat dorsal spinal cord led to a highly preferential expression of transgenes in astrocytes and microglial cells. This local and glia-targeted intervention allowed, for instance, the blockade of intracellular nuclear factor kappaB signaling pathway leading then to downregulation of the enhanced expression of several markers related to inflammation and pain, and, finally, to prolonged antihyperalgesic and antiallodynic effects. Targeted modulation of the expression of gene of interest in glial cells, closely restricted to a particular region of the spinal cord, may thus represent an interesting approach to refine the understanding of mechanisms by which spinal glial cells participate in pain processing.

Breast-conserving surgery with or without radiotherapy vs mastectomy for ductal carcinoma in situ: French Survey experience.

From March 2003 to April 2004, 77 physicians throughout France prospectively recruited 1289 ductal carcinoma in situ (DCIS) patients and collected data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). Ductal carcinoma in situ was diagnosed by mammography in 87.6% of patients. Mastectomy, conservative surgery alone (CS) and CS with radiotherapy (CS+RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Thus, 89% of patients treated by CS received adjuvant RT. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients (80% tamoxifen). Median tumour size was 14.5 mm (6, 11 and 35 mm for CS, CS+RT and mastectomy, respectively, P<0.0001). Nuclear grade was high in 21% of patients, intermediate in 38.5% and low in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS+RT) of patients. Oestrogen receptors were positive in 69.8% of assessed cases (31%). Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin and grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Precise U-Pb age constrains on the Ediacaran biota in Podolia, East European Platform, Ukraine.

The Neoproterozoic Era was characterized by rapidly changing paleogeography, global climate changes and especially by the rise and fall of the Ediacaran macro-biota. The correlation between disparate Ediacaran fossil-bearing localities and the tentative reconstruction of their paleoenvironmental and paleogeographic contexts are usually complicated by the lack of precise and accurate age data. For this reason, Neoproterozoic sedimentary sections associating Ediacaran biota fossils and fresh volcanic material are especially valuable for radioisotopic dating. Our research in the Podolya Basin, southwestern Ukraine, revealed the presence of four Neoproterozoic volcanic ash deposits (potassium-bentonite layers) within Ediacaran fossil-bearing siliciclastic rocks of the Mohyliv-Podilskyi Group. We used zircon U-Pb LA-ICPMS and CA-ID-TIMS methods to date two of those layers. The results indicate that a diverse assemblage of body and trace Ediacaran fossils occurred as early as 556.78 ± 0.18 million years (Ma) ago. By combining morphological evidence and new age determinations, we suggest a closer paleobiogeographical relationship between the Ukrainian Ediacaran assemblage and the Avalon paleocontinent than previously estimated.

Validation of a haemoglobin dilution method for estimation of blood loss.

BACKGROUND AND OBJECTIVES: Analysis of haemoglobin (Hb) dilution after bleeding is a simple, inexpensive and non-invasive method to estimate blood loss. Blood volume is estimated, taking sex, weight and height into account. The Hb concentration before and after blood loss is analysed and, from the difference, the blood loss volume can be calculated assuming a normovolemic subject. Although widely used this method has never been validated. MATERIAL AND METHODS: The Hb concentration of 21 blood donors was analysed before and up to 4 days after a standard blood donation and in another 18 blood donors the Hb concentration was analysed before and on day 4, 6, 8, 11 and 14 after blood donation. The blood volume of each donor was calculated and the donated blood volume was estimated by weighing. We calculated the blood loss by the Hb dilution method and compared the calculated value with the donated blood volume. RESULTS: The mean donated blood volume was 442 +/- 10 ml, whereas the mean calculated blood loss was 152 +/- 214 ml using the Hb concentration of the first day after donation and 301 +/- 145 ml with the Hb concentration of day 6 after blood donation after which no further Hb decrease was observed. The directly measured Hb concentration was always higher than the calculated/expected Hb concentration based on the blood donation volume. CONCLUSIONS: The Hb dilution method underestimates the true blood loss by more than 30% after a moderate blood loss of approximately 10% of the total blood volume.

[Patients' preferences and decision-making: state of the art and applications in cancer]. / Préférences des patients et prise de décision : état des lieux et retour d'expérience en cancérologie.

BACKGROUND: This paper deals with the physician-patient encounter. In France, the current legal framework allows patients to be informed (patients' rights to health information) and to participate to decisions regarding their own health. In such a context, this paper aims to give the reader the broad key components of the so-called 'patient treatment preferences elicitation process' in breast cancer, our research area. METHODS AND RESULTS: We first present the general context, with a definition of the different physician-patient models. We then present decision aids, tools that aim to provide high-quality information to patients in the decision-making process. Finally, based on our previous studies and on examples drawn from the international literature, we present the empirical process of patients' preferences elicitation, which not only increases patients' knowledge of and satisfaction with the decision made, but also allows patients to be part of their disease management. CONCLUSION: Far from being a phenomenon in the air supported by a legal system, this method developed in the 90s allows patients and more generally healthcare users to be autonomous without constraining them to a choice.

Tissue-engineered bone regeneration.

Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.

Effect of microstructure on the mechanical properties of Haversian cortical bone.

The mechanical properties of cortical bone have been extensively studied at the macrostructural scale. However, knowledge of the macroscopic mechanical properties is not sufficient to predict local phenomena, such as damage or bone remodeling, both of which are dependent on local mechanical behavior. The objective of this study is to quantify the mechanical properties of cortical bone at several length scales, with emphasis on the microstructure of Haversian systems. Samples of mature bovine cortical bone, with a Haversian microstructure, were obtained from the posterior area of the mid-femoral diaphysis. A nanoindentation technique was used to measure the local Young's modulus. The distribution of the bone mineral content was obtained by backscattered electron imaging using a scanning electron microscope. A novel compression device employing microextensometry techniques was developed to quantify local strains. Digital image correlation was performed on the microstructure imaged by optical microscopy during compression tests. This study demonstrated that the local Young's modulus and strain were heterogeneous at the scale of an osteon. For both properties, the ratio between the maximum and minimum values was approximately two. The local Young's modulus and bone-mineral content were reasonably correlated (r2 = 0.75; P < 0.0001), but this was not the case for the distribution of local strains versus bone mineral content (r2 = 0.395; P < 0.0001). Hence, local strains cannot be described simply in terms of the bone mineral content, as the Haversian canal and osteonal microstructure have a major influence on these properties. In conclusion, the microstructure must be considered in evaluating the local strain and stress fields of cortical bone.

Effects of autologous platelet lysates on ceramic particle resorption and new bone formation in critical size defects: the role of anatomical sites.

This study investigated the effects of rabbit autologous platelet lysates (APL) on the performance of fillers consisting of calcium carbonate ceramic particles (CP) pertinent to new bone formation and repair. Critical-size defects in rabbit femurs and calvaria were filled with CP alone, CP plus APL, and CP plus APL with or without thrombin (THR). After 6 weeks, resorption of CP occurred under all conditions tested in the present study. Compared with respective CP alone controls, addition of APL resulted in significantly higher ceramic resorption, as evidenced by decreased ceramic particle diameter (p < 0.01) and number (p < 0.01) at both defect sites. The presence of THR prevented reduction of both CP diameter and number in the femoral defect sites. Addition of APL to the CP resulted in a significant (p < 0.03) decrease in new bone area at the calvarial sites, but not at the femoral sites; moreover, when THR was added to the CP plus APL fillers, bone formation in the femoral defects was significantly (p < 0.05) reduced. In addition to differences in the respective anatomical and cellular milieu, the biochemical events induced by mechanical loading at the femurs may explain the reduced ceramic particle resorption as well as the enhanced new bone formation when compared with the results obtained at the calvarial defect sites.

Microfluidic separation of magnetic nanoparticles on an ordered array of magnetized micropillars.

Microfluidic separation of magnetic particles is based on their capture by magnetized microcollectors while the suspending fluid flows past the microcollectors inside a microchannel. Separation of nanoparticles is often challenging because of strong Brownian motion. Low capture efficiency of nanoparticles limits their applications in bioanalysis. However, at some conditions, magnetic nanoparticles may undergo field-induced aggregation that amplifies the magnetic attractive force proportionally to the aggregate volume and considerably increases nanoparticle capture efficiency. In this paper, we have demonstrated the role of such aggregation on an efficient capture of magnetic nanoparticles (about 80 nm in diameter) in a microfluidic channel equipped with a nickel micropillar array. This array was magnetized by an external uniform magnetic field, of intensity as low as 6-10 kA/m, and experiments were carried out at flow rates ranging between 0.3 and 30 µL/min. Nanoparticle capture is shown to be mostly governed by the Mason number Ma, while the dipolar coupling parameter α does not exhibit a clear effect in the studied range, 1.4 < α < 4.5. The capture efficiency Λ shows a strongly decreasing Mason number behavior, Λ∝Ma^{-1.78} within the range 32 ≤ Ma ≤ 3250. We have proposed a simple theoretical model which considers destructible nanoparticle chains and gives the scaling behavior, Λ∝Ma^{-1.7}, close to the experimental findings.