Treatment Responses in Histologic Versus Molecular Diagnoses of Lung Rejection.

Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment. 54 TBBs from Prague Lung Transplant Program obtained between December 2015 and January 2020 were included. Patients with acute cellular rejection (ACR) grade ≥ 1 by histology received anti-rejection treatment. Response to therapy was defined as an increase in FEV1 of ≥ 10% 4 weeks post-biopsy compared to the pre-biopsy value. Among the 54 analyzed TBBs, 25 (46%) were concordant with histology, while 29 (54%) showed discrepancies. ACR grade 0 was found in 12 TBBs (22%) and grade A1 ≥ 1 in 42 TBBs (78%). Treatment response was present in 14% in the NR group and in 50% in the TCMR group (p = 0.024). Our findings suggest that low-grade acute cellular rejection is less likely to be associated with molecular TCMR, which might better identify lung transplant recipients who benefit from therapy.

Perceptual validation of sound environment reproduction inside an aircraft mock-up.

Auditory comfort evaluations are garnering increased attention in engineering and particularly in the context of air transportation. Being able to produce sound environments corresponding to various flight conditions in aircraft mock-ups would be a valuable tool to investigate acoustic comfort inside aircrafts in controlled environments. Before using such mock-ups, they must be developed and validated in physical and perceptual terms. This paper provides a perceptual validation of sound environment reproduction inside aircraft mock-up. To provide a faithfully reproduced sound environment, time, frequency and spatial characteristics should be preserved. Physical sound field reproduction approaches for spatial sound reproduction are required while properly preserving localization cues at the listener's ears to recreate a realistic and immersing sound environment. We report a perceptual validation of a sound field reproduction system developed in an aircraft mock-up based on multichannel least-square methods and equalization. Twenty participants evaluated reproduced sound environments relative to a reference sound environment in an aircraft cabin mock-up equipped with a 41-actuator multichannel sound reproduction system. Results indicate that the preferred reproduction corresponds to the best physical reconstruction of the sound environment.

Spatio-temporal survey of small mammal-borne Trypanosoma lewisi in Cotonou, Benin, and the potential risk of human infection.

Human trypanosomoses are the sleeping sickness in Africa and Chagas disease in Latin America. However, atypical human infections by animal trypanosomes have been described, but poorly investigated. Among them, the supposed rat-specific T. lewisi was shown to be responsible for a few severe cases. In Africa, the scarcity of data and the null awareness about the atypical human trypanosomoses suggest that the number of cases may be higher that currently thought. Furthermore, T. lewisi is resistant to normal human serum and therefore a potential human pathogen. In order to document T. lewisi distribution and ecology, a qPCR- and 16DNA sequencing-based survey was conducted in 369 rodents from three urban districts of Cotonou city, Benin, during three different periods of the same year. Our study demonstrated very high prevalence (57.2%) even when considering only individuals identified as positive through DNA sequencing (39.2%). Black rats represented the most dominant as well as the most T. lewisi-parasitized species. No difference was retrieved neither between seasons nor districts, suggesting a large infestation of rodents by trypanosomes throughout the year and the city. Our results suggest that conditions are gathered for rat to human transmission of T. lewisi in these socio-environmentally degraded urban areas, thus pointing towards the rapidly urbanizing Abidjan-Lagos corridor as a region at particular risk.

Mapping responsible conduct in the uncharted field of research-creation: A scoping review.

This scoping review addresses the issues of responsible conduct of research (RCR) that can arise in the practice of research-creation (RC), an emergent, interdisciplinary, and heterogeneous field at the interface of academic research and creative activities. Little is yet known about the nature and scope of RCR issues in RC, so our study examined three questions: (1) What are the specific issues in RC in relation to RCR? (2) How does the specificity of RC influence the understanding and practice of RCR? (3) What recommendations could help address the issues highlighted in the literature? To answer these questions, we conducted a scoping review of the academic literature (n = 181 texts) dealing with RCR in RC. We found that researcher-creators faced some very different RCR challenges in comparison with their colleagues in the rest of academia. Addressing these issues is important for both the RCR and RC communities in order to ensure that the rapid development of this field occurs in line with the norms of RCR which, nonetheless, should be adapted to respect the particularities of RC and allow its contributions to the academic world.

Broad-range 16 s rDNA PCR in synovial fluid does not improve the diagnostic performance of septic arthritis in native joints in adults: cross-sectional single-center study in 95 patients.

OBJECTIVE: To evaluate the diagnostic performance of bacterial identification by broad-range polymerase chain reaction (PCR) of ribosomal DNA (rDNA) 16 s (16S rDNA PCR) for the diagnosis of septic arthritis on native joints. METHODS: Patients with acute mono or oligoarthritis who underwent synovial fluid puncture and prospective follow-up allowing definitive diagnosis (septic arthritis, crystal related disease, chronic inflammatory arthritis, undifferentiated arthritis) were recruited in this single-center study. Systematic analysis of synovial fluid included leukocytes count, search for urate and pyrophosphate crystals with polarized light microscopy, direct bacteriological examination (gram staining), bacteriological culture, and 16S rDNA PCR. RESULTS: Ninety-five patients were included, 34 of which (35.8%) had septic arthritis. Nineteen (20.0%) patients had received probabilistic antibiotic therapy prior to joint puncture. Gram + cocci infection accounted for 79.4% of septic arthritis, of which nearly half (47.1%) was caused by Staphylococcus aureus. Eight (23.5%) septic arthritis patients had a 16S rDNA PCR positive in the synovial fluid with an AUC of 0.618 (95% CI, 0.493-0.742), a sensitivity of 0.24 (95% CI, 0.12-0.40), and a specificity of 1.00 (95% CI 0.94-1.00). The diagnostic performance of 16S rDNA PCR was lower than that of direct examination (AUC at 0.691, CI 95%, 0.570-0.812), blood cultures (AUC at 0.727, CI 95%, 0.610-0.844), and culture (0.925, CI 95%, 0.856-0.994) for the diagnosis of septic arthritis. There was no difference in the positivity of 16S rDNA PCR according to previous exposure to antibiotics. CONCLUSIONS: 16 s rDNA PCR in the synovial fluid does not improve the diagnostic performance of septic arthritis on native adult joints, particularly for Gram-positive cocci infections.

Draft genome and reference transcriptomic resources for the urticating pine defoliator Thaumetopoea pityocampa (Lepidoptera: Notodontidae).

The pine processionary moth Thaumetopoea pityocampa (Lepidoptera: Notodontidae) is the main pine defoliator in the Mediterranean region. Its urticating larvae cause severe human and animal health concerns in the invaded areas. This species shows a high phenotypic variability for various traits, such as phenology, fecundity and tolerance to extreme temperatures. This study presents the construction and analysis of extensive genomic and transcriptomic resources, which are an obligate prerequisite to understand their underlying genetic architecture. Using a well-studied population from Portugal with peculiar phenological characteristics, the karyotype was first determined and a first draft genome of 537 Mb total length was assembled into 68,292 scaffolds (N50 = 164 kb). From this genome assembly, 29,415 coding genes were predicted. To circumvent some limitations for fine-scale physical mapping of genomic regions of interest, a 3X coverage BAC library was also developed. In particular, 11 BACs from this library were individually sequenced to assess the assembly quality. Additionally, de novo transcriptomic resources were generated from various developmental stages sequenced with HiSeq and MiSeq Illumina technologies. The reads were de novo assembled into 62,376 and 63,175 transcripts, respectively. Then, a robust subset of the genome-predicted coding genes, the de novo transcriptome assemblies and previously published 454/Sanger data were clustered to obtain a high-quality and comprehensive reference transcriptome consisting of 29,701 bona fide unigenes. These sequences covered 99% of the cegma and 88% of the busco highly conserved eukaryotic genes and 84% of the busco arthropod gene set. Moreover, 90% of these transcripts could be localized on the draft genome. The described information is available via a genome annotation portal (http://bipaa.genouest.org/sp/thaumetopoea_pityocampa/).

OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer.

Background: The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (i.p.) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC). Patients and methods: We carried out a multicenter, two-stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (i.v.) NACT followed by optimal (<1 cm) debulking surgery were randomized to one of the three treatment arms: (i) i.v. carboplatin/paclitaxel, (ii) i.p. cisplatin plus i.v./i.p. paclitaxel, or (iii) i.p. carboplatin plus i.v./i.p. paclitaxel. The primary end point was 9-month progressive disease rate (PD9). Secondary end points included progression-free survival (PFS), overall survival (OS), toxicity, and quality of life (QOL). Results: Between 2009 and 2015, 275 patients were randomized; i.p. cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared i.v. carboplatin/paclitaxel (n = 101) with i.p. carboplatin, i.v./i.p. paclitaxel (n = 102). The intention to treat PD9 was lower in the i.p. carboplatin arm compared with the i.v. carboplatin arm: 24.5% (95% CI 16.2% to 32.9%) versus 38.6% (95% CI 29.1% to 48.1%) P = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57-1.17); P = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) P = 0.40. The i.p. carboplatin-based regimen was well tolerated with no reduction in QOL or increase in toxicity compared with i.v. administration alone. Conclusion: In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, i.p. carboplatin-based chemotherapy is well tolerated and associated with an improved PD9 compared with i.v. carboplatin-based chemotherapy. Clinical trial number: clinicaltrials.gov, NCT01622543.

The conservation significance of natural hybridisation in Mediterranean plants: from a case study on Cyclamen (Primulaceae) to a general perspective.

Hybridisation plays a prominent role in plant evolution due to its influence on genetic diversity, fitness and adaptive potential. We identify a case of on-going hybrid evolution of floral phenotypes in disjunct populations of Cyclamen balearicum and C. repandum subsp. repandum on Corsica and Sardinia. Hybrid populations on the two islands contain similar patterns of variation in flower colour and size but are probably at different stages in the evolutionary process of hybridisation, and differences in the frequency of floral types and flower size suggest hybrid vigour that may contribute to the dynamics and maintenance of hybrid forms. In a review of cases of hybridisation in Mediterranean plants we found an equivalent number of cases for the contemporary occurrence of mixed hybrid populations, as there are cases of homoploid hybrid species differentiation. We argue for the development of a conservation strategy for Mediterranean plants that integrates the need to protect not just pure endemic species (some of hybrid origin) but also mixed populations where adaptive variation and new species are evolving due to contemporary hybridisation.

Source sparsity control of sound field reproduction using the elastic-net and the lasso minimizers.

Sound field reproduction is aimed at the reconstruction of a sound pressure field in an extended area using dense loudspeaker arrays. In some circumstances, sound field reproduction is targeted at the reproduction of a sound field captured using microphone arrays. Although methods and algorithms already exist to convert microphone array recordings to loudspeaker array signals, one remaining research question is how to control the spatial sparsity in the resulting loudspeaker array signals and what would be the resulting practical advantages. Sparsity is an interesting feature for spatial audio since it can drastically reduce the number of concurrently active reproduction sources and, therefore, increase the spatial contrast of the solution at the expense of a difference between the target and reproduced sound fields. In this paper, the application of the elastic-net cost function to sound field reproduction is compared to the lasso cost function. It is shown that the elastic-net can induce solution sparsity and overcomes limitations of the lasso: The elastic-net solves the non-uniqueness of the lasso solution, induces source clustering in the sparse solution, and provides a smoother solution within the activated source clusters.

Rodent-borne Trypanosoma from cities and villages of Niger and Nigeria: A special role for the invasive genus Rattus?

Although they are known to sometimes infect humans, atypical trypanosomes are very poorly documented, especially in Africa where one lethal case has yet been described. Here we conducted a survey of rodent-borne Trypanosoma in 19 towns and villages of Niger and Nigeria, with a special emphasis on Niamey, the capital city of Niger. The 1298 rodents that were captured yielded 189 qPCR-positive animals from 14 localities, thus corresponding to a 14.6% overall prevalence. Rats, especially black rats, displayed particularly elevated prevalence (27.4%), with some well sampled sites showing 40-50% and up to 68.8% of Trypanosoma-carrying individuals. Rattus were also characterized by significantly lower Ct values than in the other non-Rattus species. DNA sequences could be obtained for 43 rodent-borne Trypanosoma and corresponded to 41 T. lewisi (all from Rattus) and 2 T. microti (from Cricetomys gambianus). These results, together with data compiled from the available literature, suggest that Rattus may play a particular role for the maintaining and circulation of Trypanosoma, especially T. lewisi, in Africa. Taken into account its strong abilities to invade coastal and inland regions of the continent, we believe that this genus deserves a particular attention in regards to potentially under-looked but emerging atypical trypanosome-related diseases.

Activation of Akt/FKHR in the medulla oblongata contributes to spontaneous respiratory recovery after incomplete spinal cord injury in adult rats.

After incomplete spinal cord injury (SCI), patients and animals may exhibit some spontaneous functional recovery which can be partly attributed to remodeling of injured neural circuitry. This post-lesion plasticity implies spinal remodeling but increasing evidences suggest that supraspinal structures contribute also to the functional recovery. Here we tested the hypothesis that partial SCI may activate cell-signaling pathway(s) at the supraspinal level and that this molecular response may contribute to spontaneous recovery. With this aim, we used a rat model of partial cervical hemisection which injures the bulbospinal respiratory tract originating from the medulla oblongata of the brainstem but leads to a time-dependent spontaneous functional recovery of the paralyzed hemidiaphragm. We first demonstrate that after SCI the PI3K/Akt signaling pathway is activated in the medulla oblongata of the brainstem, resulting in an inactivation of its pro-apoptotic downstream target, forkhead transcription factor (FKHR/FOXO1A). Retrograde labeling of medullary premotoneurons including respiratory ones which project to phrenic motoneurons reveals an increased FKHR phosphorylation in their cell bodies together with an unchanged cell number. Medulla infusion of the PI3K inhibitor, LY294002, prevents the SCI-induced Akt and FKHR phosphorylations and activates one of its death-promoting downstream targets, Fas ligand. Quantitative EMG analyses of diaphragmatic contractility demonstrate that the inhibition of medulla PI3K/Akt signaling prevents spontaneous respiratory recovery normally observed after partial cervical SCI. Such inhibition does not however affect either baseline contractile frequency or the ventilatory reactivity under acute respiratory challenge. Together, these findings provide novel evidence of supraspinal cellular contribution to the spontaneous respiratory recovery after partial SCI.

Role of near-field enhancement in plasmonic laser nanoablation using gold nanorods on a silicon substrate: comment.

In this comment, we argue that the conlusion made by Harrisson and Ben-Yakar [Opt. Express 18, 22556 (2010)], which states that nanoablation with plasmonic nanorods depends on the enhancement of the Poynting vector rather than the one of the square of the electric field, is incorrect and not necessarily needed to explain their experimental results.

Permanent genetic resources added to Molecular Ecology Resources Database 1 October 2010-30 November 2010.

This article documents the addition of 277 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Ascochyta rabiei, Cambarellus chapalanus, Chionodraco hamatus, Coptis omeiensis, Cynoscion nebulosus, Daphnia magna, Gerbillus nigeriae, Isurus oxyrinchus, Lates calcarifer, Metacarcinus magister, Oplegnathus fasciatus, Pachycondyla verenae, Phaethon lepturus, Pimelodus grosskopfii, Rotylenchulus reniformis, Scomberomorus niphonius, Sepia esculenta, Terapon jarbua, Teratosphaeria cryptica and Thunnus obesus. These loci were cross-tested on the following species: Austropotamobius italicus, Cambarellus montezumae, Cambarellus puer, Cambarellus shufeldtii, Cambarellus texanus, Chionodraco myersi, Chionodraco rastrospinosus, Coptis chinensis, Coptis chinensis var. brevisepala, Coptis deltoidea, Coptis teeta, Orconectes virilis, Pacifastacus leniusculus, Pimelodus bochii, Procambarus clarkii, Pseudopimelodus bufonius, Rhamdia quelen, Sepia andreana, Sepiella maindroni, Thunnus alalunga, Thunnus albacares, Thunnus maccoyii, Thunnus orientalis, Thunnus thynnus and Thunnus tonggol.

Nasal OEC transplantation promotes respiratory recovery in a subchronic rat model of cervical spinal cord contusion.

Engraftment of nasal olfactory ensheathing cells (OEC) is considered as a promising therapeutic strategy for spinal cord repair and one clinical trial has already been initiated. However, while the vast majority of fundamental studies were focused on the recovery of locomotor function, the efficiency of this cellular tool for repairing respiratory motor dysfunction, which affects more than half of paraplegic/tetraplegic patients, remains unknown. Using a rat model that mimics the mechanisms encountered after a cervical contusion that induces a persistent hemi-diaphragmatic paralysis, we assessed the therapeutic efficiency of a delayed transplantation (2 weeks post-contusion) of nasal OECs within the injured spinal cord. Functional recovery was quantified with respiratory behavior tests, diaphragmatic electromyography and neuro-electrophysiological recording of the phrenic motoneurons while axogenesis was evaluated using immunohistochemistry. We show that 3 months post-transplantation, nasal OECs improve i) breathing movements, ii) activities of the ipsilateral diaphragm and corresponding phrenic nerve, and iii) axonal sprouting in the injury site. We also demonstrate that this functional partial recovery is mediated by the restoration of ipsilateral supraspinal command. Our study brings further evidence that olfactory ensheathing cells could have clinical application especially in tetraplegic patients with impaired breathing movements. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

Plio-Pleistocene history of West African Sudanian savanna and the phylogeography of the Praomys daltoni complex (Rodentia): the environment/geography/genetic interplay.

Rodents of the Praomys daltoni complex are typical inhabitants of the Sudanian savanna ecosystem in western Africa and represent a suitable model for testing the effects of Quaternary climatic oscillations on extant genetic variation patterns. Phylogeographical analyses of mitochondrial DNA sequences (cytochrome b) across the distribution range of the complex revealed several well-defined clades that do not support the division of the clade into the two species currently recognized on the basis of morphology, i.e. P. daltoni (Thomas, 1892) and Praomys derooi (Van der Straeten & Verheyen 1978). The observed genetic structure fits the refuge hypothesis, suggesting that only a small number of populations repeatedly survived in distinct forest-savanna mosaic blocks during the arid phases of the Pleistocene, and then expanded again during moister periods. West African rivers may also have contributed to genetic differentiation, especially by forming barriers after secondary contact of expanding populations. The combination of three types of genetic markers (mtDNA sequences, microsatellite loci, cytogenetic data) provides evidence for the presence of up to three lineages, which most probably represent distinct biological species. Furthermore, incongruence between nuclear and mtDNA markers in some individuals unambiguously points towards a past introgression event. Our results highlight the importance of combining different molecular markers for an accurate interpretation of genetic data.

[Two cases of cutaneous erythema following spinal cord stimulation]. / Erythème cutané provoqué par une neurostimulation cordonale postérieure: deux observations.

INTRODUCTION: Cutaneous complications following implantation of an electric system have been reported mainly after the implantation of pacemakers, cardiac defibrillators and morphine pumps. However, cutaneous complications following implantation of spinal cord stimulators are rarely described in the literature. Here we report two cases of cutaneous eruption at the spinal cord stimulation site, one involving foreign-body reaction to silicone in the neurostimulator electrodes or connector block and the other comprising contact dermatitis to silicone. CASE REPORTS: Case 1: A 43-year-old woman had been implanted with a spinal cord stimulator. Four months after implantation, burning sensation and cutaneous inflammatory erythema were observed in the dorsolumbar region, with reduced efficiency of stimulation. Removal of the neurostimulator led to resolution of the cutaneous symptoms. Histopathological examination of the biopsy sample showed foreign-body granuloma formation. The same symptoms subsequently recurred on the surgical scar and histopathology showed granuloma formation in response to particles of silicone present in the connector. The cutaneous eruption subsided rapidly after excision. Case 2: In a 60-year-old man implanted with a spinal cord stimulator, pruriginous reticular erythema was rapidly observed on the skin just above the neurostimulator, with papules around the erythema. Histopathology of two cutaneous biopsies showed evidence of contact dermatitis. Skin-patch tests performed with components of the neurostimulator leads proved positive to two types of silicone after 72 hours. The eruption was successfully controlled using topical corticosteroid therapy. DISCUSSION: Reports of cutaneous eruptions after spinal cord stimulation are extremely rare. Here we report two different cutaneous reactions with two different pathophysiological mechanisms, both involving silicone. The first case is original because it is the first documented case of a foreign-body reaction involving granuloma formation in response to particles of silicone present in the components of a neurostimulator. The second case concerns contact dermatitis to silicone (present in the connector block and electrode sheaths).

Geographic patterns of inversion polymorphisms in a wild African rodent, Mastomys erythroleucus.

By suppressing recombination and reducing gene flow, chromosome inversions favor the capture and protection of advantageous allelic combinations, leading to adaptive polymorphisms. However, studies in non-model species remain scarce. Here we investigate the distribution of inversion polymorphisms in the multimammate rat Mastomys erythroleucus in West Africa. More than 270 individuals from 52 localities were karyotyped using G-bands and showed widespread polymorphisms involving four chromosome pairs. No significant deviations from Hardy-Weinberg equilibrium were observed either through space or time, nor were differences retrieved in viability or sex contribution between cytotypes. The distribution of chromosomal variation, however, showed perfect congruence with that of mtDNA-based phylogeographic clades. Thus, inversion diversity patterns in M. erythroleucus appeared more related to historical and/or demographic processes than to climate-based adaptive features. Using cross-species chromosome painting and G-banding analyses to identify homologous chromosomes in related out-group species, we proposed a phylogenetic scenario that involves ancestral-shared polymorphisms and subsequent lineage sorting during expansion/contraction of West African savannas. Our data suggest that long-standing inversion polymorphisms may act as regions in which adaptation genes may accumulate (nucleation model).

Outcome of uterine clear cell carcinomas compared to endometrioid carcinomas and poorly-differentiated endometrioid carcinomas.

OBJECTIVES: Our aim was to compare the survival between patients with clear cell carcinoma (CC) and patients with endometrioid carcinoma (EC). METHODS: Through the population-based Geneva Cancer Registry, we identified 1,380 resident women diagnosed with uterine cancer between 1970 and 2000. We excluded those with papillary serous endometrial carcinoma and uterine sarcomas. We categorized patients as CC (n = 32, 2.8%) or EC (n = 1,145, 97.2%). Uterine cancer-specific survival rates were calculated by Kaplan-Meier analysis. We used Cox proportional hazards analysis to compare uterine cancer mortality risks between groups, and adjusted these risks for other prognostic factors. RESULTS: CC patients presented with a more advanced stage at diagnosis than EC patients (p = 0.002). Compared to women with EC, women with CC had a significantly greater risk of dying from their disease (hazard ratio [HR] 2.9, 95% confidence interval (95% CI) 1.7-4.9). After adjustment for age, stage and adjuvant chemotherapy, the risk of dying from uterine cancer was still significantly higher for CC patients (HR 2.0, 95% CI 1.2-3.4). By univariate analysis, the risk of dying of endometrial cancer was not significantly higher in CC patients than in patients with poorly-differentiated EC (HR 1.3, 95% CI 0.7-2.3). CONCLUSION: This population-based investigation shows that patients with CC have a poorer outcome than those with EC. Studies to determine the role of adjuvant treatment in CC patients are needed.

Diaphragm recovery by laryngeal innervation after bilateral phrenicotomy or complete C2 spinal section in rats.

This study aimed to highlight the functional aspects of diaphragm reinnervation by laryngeal motoneurons after bilateral phrenicotomy or complete cervical transection. The left recurrent laryngeal nerve was connected to the left phrenic nerve in 14 rats. Five months later, all bridged rats presented a substantial ipsilateral diaphragm recovery (74.2 +/- 10% of contralateral activity) whereas the diaphragm remained paralysed in non-bridged rats (n = 5/5). After additional right phrenicotomy, functional breathing persisted in bridged rats whereas all non-bridged died. After complete C2 spinal transection, diaphragm respiratory discharges persisted in bridged rats. The reinnnervation by laryngeal motoneurons was confirmed by retrograde labeling, stimulus-elicited diaphragm response by vagal stimulation and diaphragm inactivation after vagotomy. In conclusion, the recurrent-phrenic nerve anastomosis induces a reliable functional diaphragm outcome even after contralateral diaphragm denervation or complete high cervical spinal cord injury, and could be considered as a clinical repair strategy for re-establishing diaphragm autonomy following spinal cord trauma.