Feature tracking cardiovascular magnetic resonance reveals recovery of atrial function after acute myocarditis.

Follow-up after acute myocarditis is important to detect persisting myocardial dysfunction. However, recovery of atrial function has not been evaluated after acute myocarditis so far. Thirty-five patients with strictly defined acute myocarditis underwent cardiovascular magnetic resonance (CMR, 1.5 T) in the acute stage at baseline (BL) and at 3 months follow-up (FU). The study population included 13 patients with biopsy-proven "cardiomyopathy-like" myocarditis (CLM) and 22 patients with "infarct-like" (ILM) clinical presentation. CMR feature tracking (FT) was performed on conventional cine SSFP sequences. Median LA-GLS increased from 33.2 (14.5; 39.2) at BL to 37.0% (25.2; 44.1, P = 0.0018) at FU in the entire study population. Median LA-GLS also increased from 36.7 (26.5; 42.3) at BL to 41.3% (34.5; 44.8, P = 0.0262) at FU in the ILM subgroup and from 11.3 (6.4; 21.1) at BL to 21.4% (14.2; 30.7, P = 0.0186) at FU in the CLM subgroup. Median RA-GLS significantly increased from BL with 30.8 (22.5; 37.0) to FU with 33.7% (26.8; 45.4, P = 0.0027) in the entire study population. Median RA-GLS also significantly increased from 32.7 (25.8; 41.0) at BL to 35.8% (27.7; 48.0, P = 0.0495) at FU in the ILM subgroup and from 22.8 (13.1; 33.9) at BL to 31.0% (26.0; 40.8, P = 0.0266) at FU in the CLM subgroup. Our findings demonstrate recovery of LA and RA function by CMR-FT strain analyses in patients after acute myocarditis independent from clinical presentation. Monitoring of atrial strain could be an important tool for an individual assessment of healing after acute myocarditis.

Human factor associations with safety events in radiation therapy.

BACKGROUND AND PURPOSE: Incident learning can reveal important opportunities for safety improvement, yet learning from error is challenged by a number of human factors. In this study, incident learning reports have been analyzed with the human factors analysis classification system (HFACS) to uncover predictive patterns of human contributing factors. MATERIALS AND METHODS: Sixteen hundred reports from the Safety in Radiation Oncology incident learning system were filtered for inclusion ultimately yielding 141 reports. A radiotherapy-specific error type was assigned to each event as were all reported human contributing factors. An analysis of associations between human contributing factors and error types was performed. RESULTS: Multiple associations between human factors were found. Relationships between leadership and risk were demonstrated with supervision failures. Skill-based errors (those done without much thought while performing familiar tasks) were found to pose a significant safety risk to the treatment planning process. Errors made during quality assurance (QA) activities were associated with decision-based errors which indicate lacking knowledge or skills. CONCLUSION: An application of the HFACS to incident learning reports revealed relationships between human contributing factors and radiotherapy errors. Safety improvement efforts should include supervisory influences as they affect risk and error. An association between skill-based and treatment planning errors showed a need for more mindfulness in this increasingly automated process. An association between decision and QA errors revealed a need for improved education in this area. These and other findings can be used to strategically advance safety.

[Extreme hypofractionated radiation therapy for pancreatic cancer]. / Radiothérapie hypofractionnée extrême du cancer du pancréas.

Pancreatic cancer has poor prognosis and a continuously growing incidence. By 2030, it should become the second cause of death by cancer worldwide and in France. The only curative treatment is surgery that is achievable in only 20% of patients at the time of initial diagnosis, with a high rate of incomplete resection. Neoadjuvant treatments using chemotherapy with or without radiotherapy are more often admitted to play an important role by selecting non-progressing cases who will benefit from surgery, by increasing the number of complete resection, and by making locally advanced and borderline tumours accessible to resection. However, the role of radiotherapy is still debated. Because of its dosimetric advantages, its short total duration, and its good tolerance with reduced volumes of irradiation, stereotactic radiotherapy has been largely studied. Compared to chemoradiotherapy, this technique could improve the therapeutic index helping to preserve the general status of patients in order to give them access to secondary surgery. It remains a promising technique still under evaluation, to be delivered ideally, as part of a clinical trial, or within an experimented team.

Salvage brachytherapy as a modern reirradiation technique for local cancer failure: The Phoenix is reborn from its ashes.

The treatment of local recurrence of a previously irradiated cancer or a second cancer arising in-field remains challenging. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Reirradiation has historically been associated with unacceptable toxicity and a limited benefit. Brachytherapy offers the best dose distribution and a high radiation dose to the target volume while better protecting surrounding previously irradiated healthy tissues. The management of local cancer recurrence in irradiated areas should be planned through multidisciplinary discussions and patients should be selected carefully. This overview of the literature describes brachytherapy as a reirradiation treatment in local recurrences of previously irradiated prostate, breast, head and neck and rectal cancers, or second primary cancers occurring in-field. For these cancers, the prognosis and therapeutic challenges are quite different and depend on the type of primary cancer. However, current data confirm that brachytherapy reirradiation is feasible and has acceptable toxicity.

Shoulder patient-specific guide: First experience in 10 patients indicates room for improvement.

BACKGROUND: Implantation of the glenoid component of a total shoulder prosthesis can be facilitated by using a patient-specific guide (PSG) designed to ensure replication of the preoperatively planned position. The objective of this study was to assess the reliability and accuracy of a PSG in replicating the planned glenoid component position during total shoulder arthroplasty (TSA). HYPOTHESIS: Additional criteria should be used for 3D preoperative planning and PSG design to further improve the accuracy of glenoid component positioning. MATERIAL AND METHODS: We studied 10 patients who underwent TSA with use of a PSG to position the glenoid component after preoperative 3D planning. Postoperative glenoid version and tilt were measured and compared to the planned values. We also used new criteria to assess implant rotation and global 3D position, as well as accuracy of the 3D pilot hole for the glenoid guide-pin. RESULTS: Mean errors in glenoid position were -1.7°±4.4° for version, -0.4°±4.9° for tilt, and 6.0°±13.5° for rotation. Mean difference in global orientation of the glenoid implant versus the planned value was 4.9°±2.5°. Mean 3D discrepancy in glenoid pilot hole position was 2.9±0.5mm; the discrepancy was greater in the mediolateral direction (1.9±0.9mm) than in the supero-inferior (1.1±1.2mm) and antero-posterior (0.8±1.2mm) directions. DISCUSSION: The poor performance of the PSG in controlling rotation and reaming may explain the difference in global glenoid position compared to the planned value. Improvements in PSG design to incorporate these two parameters deserve consideration. LEVEL OF EVIDENCE: II, prospective cohort study.

Endoscopic ulnar nerve release at the elbow: Indications and outcomes.

BACKGROUND: Ulnar nerve entrapment at the elbow is the second most common nerve entrapment syndrome at the upper limp, after carpal tunnel syndrome. Many surgeons feel that ulnar nerve instability contra-indicates endoscopic nerve release. Published studies, however, found no evidence that pre-operative or intra-operative ulnar nerve instability adversely affected clinical outcomes. The objective of this prospective study was to define the indications and describe the outcomes of endoscopic ulnar nerve release at the elbow. HYPOTHESIS: Endoscopic ulnar nerve release at the elbow is a valid option even in patients with ulnar nerve instability and regardless of the severity of the compression. MATERIAL AND METHODS: We conducted a prospective single-centre study of patients scheduled for surgery based on clinical and electromyographic manifestations of ulnar nerve entrapment at the elbow. Ulnar nerve instability (incomplete dislocation, i.e., Childress A) before or during surgery was not a contra-indication to the procedure. The patients were re-evaluated 12 months after surgery. RESULTS: Seventeen patients were included in the statistical analysis. The modified Bishop's score indicated excellent or good outcomes in 15 (88%) patients (excellent in 4 and good in 11) and a fair outcome in 2 patients. Functional outcomes were not associated with the presence of ulnar nerve instability before surgery. DISCUSSION: We elected to include patients with Childress A ulnar nerve instability. Clinical outcomes in these patients were similar to those in patients without ulnar nerve instability. LEVEL OF EVIDENCE: IV, open prospective study of treatment outcomes.

The respiratory DC/macrophage network at steady-state and upon influenza infection in the swine biomedical model.

Human and mouse respiratory tracts show anatomical and physiological differences, which will benefit from alternative experimental models for studying many respiratory diseases. Pig has been recognized as a valuable biomedical model, in particular for lung transplantation or pathologies such as cystic fibrosis and influenza infection. However, there is a lack of knowledge about the porcine respiratory immune system. Here we segregated and studied six populations of pig lung dendritic cells (DCs)/macrophages (Mθs) as follows: conventional DCs (cDC) 1 and cDC2, inflammatory monocyte-derived DCs (moDCs), monocyte-derived Mθs, and interstitial and alveolar Mθs. The three DC subsets present migratory and naive T-cell stimulation capacities. As observed in human and mice, porcine cDC1 and cDC2 were able to induce T-helper (Th)1 and Th2 responses, respectively. Interestingly, porcine moDCs increased in the lung upon influenza infection, as observed in the mouse model. Pig cDC2 shared some characteristics observed in human but not in mice, such as the expression of FCɛRIα and Langerin, and an intra-epithelial localization. This work, by unraveling the extended similarities of the porcine and human lung DC/Mθ networks, highlights the relevance of pig, both as an exploratory model of DC/Mθ functions and as a model for human inflammatory lung pathologies.

Systematic screening for PRKAR1A gene rearrangement in Carney complex: identification and functional characterization of a new in-frame deletion.

BACKGROUND: Point mutations of the PRKAR1A gene are a genetic cause of Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD), but in 30% of the patients no mutation is detected. OBJECTIVE: Set up a routine-based technique for systematic detection of large deletions or duplications of this gene and functionally characterize these mutations. METHODS: Multiplex ligation-dependent probe amplification (MLPA) of the 12 exons of the PRKAR1A gene was validated and used to detect large rearrangements in 13 typical CNC and 39 confirmed or putative PPNAD without any mutations of the gene. An in-frame deletion was characterized by western blot and bioluminescence resonant energy transfer technique for its interaction with the catalytic subunit. RESULTS: MLPA allowed identification of exons 3-6 deletion in three patients of a family with typical CNC. The truncated protein is expressed, but rapidly degraded, and does not interact with the protein kinase A catalytic subunit. CONCLUSIONS: MLPA is a powerful technique that may be used following the lack of mutations detected by direct sequencing in patients with bona fide CNC or PPNAD. We report here one such new deletion, as an example. However, these gene defects are not a frequent cause of CNC or PPNAD.

Decompaction and fluidization of a saturated and confined granular medium by injection of a viscous liquid or gas.

We compare quantitatively two experimental situations concerning injection of a miscible fluid into an initially jammed granular medium saturated with the same fluid, confined in a Hele-Shaw cell. The two experiments are identical, apart from the interstitial and injected fluid, which is in one case air injected into a dry granular packing, and in the other case silicone oil injected into a dense suspension. In spite of the strong differences regarding the nature of the two fluids, strikingly similar dynamical and geometrical features are identified as functions of the control parameters: cell thickness and applied fluid injection pressure. In both cases an initial hydrodynamically driven decompaction process controls the unjamming and prepares the final displacement process characterized by fingerlike patterns empty of grains. The pattern shapes are comparable. In addition, the mobilities of the coupled fluid-grain flow, rescaled by the interstitial fluid viscosity and grain diameter squared, are of the same range and behave comparably. The mobility proves to depend on the initial solid fraction of the medium. Subtle differences are observed in geometrical aspects like the finger width with respect to the control parameters.

Human osteosarcoma cells express functional receptor activator of nuclear factor-kappa B.

RANK, RANK ligand (RANKL) and osteoprotegerin (OPG) are the key regulators of bone metabolism, both in normal and pathological conditions. Previous data have demonstrated that human osteosarcoma biopsies express RANKL as well as OPG, and functional RANK is expressed in a murine osteosarcoma cell line. As RANK expression in human osteosarcoma remains controversial, the aim of the present study was to analyse its expression in vitro in human osteosarcoma cell lines, ex vivo using pathological tissues, and then to determine its functionality in terms of signal transduction pathways modulated by RANKL. RT-PCR analysis and immunohistochemistry experiments revealed that RANK is expressed at both transcriptional and protein levels in MNNG/HOS, Saos-2 and MG-63 human osteosarcoma cell lines, in contrast to the U-2 OS osteosarcoma cell line and human osteoblasts, which were negative. RANK was also expressed in 57% of osteosarcoma biopsies. Furthermore, western blot experiments clearly demonstrated the functionality of RANK. Thus, RANKL significantly induced the phosphorylation of ERK1/2, p38 and IkappaB in RANK-positive osteosarcoma cells. This study is the first report of functional RANK expression in human osteosarcoma cells: this strengthens the involvement of the RANK-RANKL-OPG axis in primary bone tumour biology and identifies novel therapeutic approaches targeting RANK-positive osteosarcoma.

Effects of fasting and refeeding on jejunal morphology and cellular activity in rats in relation to depletion of body stores.

BACKGROUND: Intestinal mucosa atrophy following a period of starvation characterized by the mobilization of fat stores for energy expenditure (phase II) worsen after a long fast marked by an increase in protein catabolism (phase III). However, the morphology of the jejunum is completely restored after 3 days of refeeding. The aim of this study was to determine the mechanisms involved in the rapid jejunal restoration following the critical phase III. METHODS: Jejunal structure was observed through conventional and environmental scanning electron microscopy, whilst cellular dynamics were studied using classical optic microscopy tools and immunohistochemistry. RESULTS: Mucosal structural atrophy during fasting proved to worsen over the two phases. During phase II, apoptosis is still present at the tip of the villi, the number of mitosis in crypts showed a 30% decrease and a transient drop in cell migration is observed. During phase III, however, an 85% rise in mitosis was noticed along with an increase in cell migration and the disappearance of apoptotic cells at the villus tips. This increased cell renewal continues after food ingestion. CONCLUSIONS: Starved rats appeared to be in a phase of energy sparing in phase II, with depressed cellular events in the intestinal mucosa. In phase III, however, the preservation of functional cells and the early increase in crypt cell proliferation should prepare the mucosa to refeeding and could explain why jejunal repairs are complete after 3 days of refeeding following either phase II or phase III.

Intralipid 10%: physicochemical characterization.

OBJECTIVES: Parenteral fat emulsions contain two populations of particles: artificial chylomicrons rich in triacylglycerols (TAG), and liposomes (bilayer of phospholipids [PL] enveloping an aqueous phase). Centrifugation permits isolating the liposomes in the infranatant called mesophase. The aim of the present work was to better characterize this mesophase chemically and to view the particles it contains by electron microscopy. METHODS: Electron microscopy (Philips 410) was performed after cryofracture on native 10% Intralipid, mesophase (centrifugation for 1 h at 27 000 g), and a liposome-enriched fraction (ring of density 1.010-1.030 g/l obtained after centrifuging mesophase in a KBr density gradient at 100 000 g for 24 h). The TAG and protein content of the mesophase was analyzed and the proteins partially characterized by immunodetection (Western-blot). RESULTS: This electron microscope study of 10% Intralipid gives evidence for the coexistence of artificial chylomicrons (mean diameter, 260 nm) and liposomes (43 nm), the latter being smaller than expected and containing 8% w/w TAG after purification. The solubilization of TAG in PL bilayers (reported to be < or = 3.1% w/w) might have been increased in parenteral emulsions by the manufacturing process or/and the high TAG/PL ratio. Minute amounts of proteins have also been detected and partially characterized using a specific antibody raised against the human 7 kDa Anionic Polypeptide Factor (APF), known to strongly interact with PL in bile. CONCLUSIONS: This work has shown that the size (mean diameter, 43 nm) of the liposomes present in 10% Intralipid is smaller than that usually assumed. Traces of hydrophobic proteins in the emulsion may account for certain allergic reactions sometimes observed in infused patients.

Intracellular vesicular trafficking in the gill epithelium of urea-excreting fish.

Most teleost fish are ammoniotelic, and relatively few are ureotelic, in which the majority of nitrogenous waste is excreted as urea. This study aimed to determine whether the gill ultrastructure of ureotelic fish might have specific, unique characteristics compared with ammoniotelic fish. The gill morphology was studied in three closely related species of the family Batrachoididae: Opsanus beta, the gulf toadfish; Opsanus tau, the oyster toadfish; and Porichthys notatus, the plainfin midshipman, because prior studies have demonstrated that the two former species are ureotelic and excrete urea in unique, short daily pulses, whereas the latter is ammoniotelic. Ultrastructural studies demonstrated significant trafficking of dense-cored vesicles (50-200 nm) between the Golgi apparatus and the apical membrane of epithelial cells surrounding gill filaments and lamellae in these two Opsanus spp. The material constituting the core of these vesicles was intensely stained by lead salt and was unloaded externally when vesicles contacted the apical membrane. Another characteristic of these urea-secreting fish was the presence of numerous large, black-stained lysosomes, which contained cored vesicles, suggesting a second destination for the dense-cored vesicles. As a working hypothesis, the present data suggest that the urea-transporter protein, recently found in toadfish gills, is inserted in the vesicle. Subsequently, it could serve to either sequester cytosolic urea that ultimately is secreted into the water after contact of these vesicles with the pavement cell apical membrane, or it could allow facilitated diffusion of urea across the plasma membrane following insertion into the membrane. As further comparative evidence, the ammoniotelic P. notatus exhibited neither the vesicular trafficking nor the population of lysosomes both found in Opsanus spp.

Endoreduplication in higher plants.

Cell polyploidisation can be achieved by endoreduplication, which consists of one or several rounds of DNA synthesis in the absence of mitosis. As a consequence, chromosomes with 2n chromatids are produced without change in the chromosome number. Endoreduplication is the most common mode of polyploidisation in plants and can be found in many cell types, especially in those undergoing differentiation and expansion. Although accumulating data reveal that this process is developmentally regulated, it is still poorly understood in plants. At the molecular level, the increasing knowledge on plant cell cycle regulators allows the acquisition of new tools and clues to understand the basis of endoreduplication control and, in particular, the switch between cell proliferation and cell differentiation.

Molecular cloning and characterization of six cDNAs expressed during glucose starvation in excised maize (Zea mays L.) root tips.

In order to isolate glucose-starvation-related cDNAs in maize (Zea mays L.) root tips, a cDNA library was constructed with poly(A)+ mRNA from 24 h starved root tips. After differential screening of the library, we isolated six different cDNAs (named pZSS2 and pZSS7) which were expressed during glucose starvation. Time course analysis revealed that maximum expression of five of these genes occurs 30 h after the onset of the starvation treatment. On the contrary, the expression of mRNAs corresponding to pZSS4 was maximal at an early stage of starvation and then dramatically decreased. The expression of this gene did not seem to be specific for glucose starvation. The pattern of induction of the genes corresponding to pZSS2, pZSS3, pZSS5, pZSS6 and pZSS7 revealed that non-metabolizable sugars such as L-glucose and mannitol induce mRNA transcription similarly to glucose starvation. When D-glucose or any other metabolizable sugar was supplied, the level of transcripts was reduced. Nucleotide sequence analyses of the six cDNAs allowed identification of five of them by comparison with sequence data bases. The protein encoded by clone pZSS2 is analogous to a wound-induced protein from barley. Clones pZSS4 to pZSS7 encode, respectively, a transmembrane protein, a cysteine protease, a metallothionein-like protein and a chymotrypsin/subtilisin-like protease inhibitor. Clone pZSS3 shares no significant homology with any known sequence.

[Morphological characterization of cell lines of human uveal melanoma]. / Caractérisation morphologique de lignées cellulaires de mélanome uvéal humain.

Several cell lines have been derived from an ocular melanoma obtained from an enucleated patient. Three cell types are observed during the time in culture of all the cell lines under study. Two of them have epithelial and spindle shape respectively. A third cell type, having a spheroidal shape, is formed from spindle cells and may be transformed into epithelial cells upon re-seeding. Further experiments showed that the same cell may change of shape following the cycle: spheroidal-->epithelial-->fusiform-->spheroidal. Scanning microscopy shows the coexistence of the three cell shapes in the same culture and the presence of several filaments and processes protruding at the surface of the cells. Transmission electron microscopy shows that the cell lines, in general, contain melanosomes empty or fairly pigmented and several filaments and microtubules. The presence of melanin may be stimulated by seeding of melanoma cells over a "feeder layer" of fibroblasts.

Complete amino acid sequence of puroindoline, a new basic and cystine-rich protein with a unique tryptophan-rich domain, isolated from wheat endosperm by Triton X-114 phase partitioning.

A new basic protein has been isolated from wheat endosperm by Triton X-114 phase partitioning. It contains five disulfide bridges and is composed of equal amounts of a polypeptide chain of 115 amino acid residues and of the same chain with a C-terminus dipeptide extension. The most striking sequence feature is the presence of a unique tryptophan-rich domain so that this protein isolated from wheat seeds has been named puroindoline. The similar phase partitioning behavior in Triton X-114 of this basic cystine-rich protein and of purothionins suggests that puroindoline may also be a membranotoxin that might play a role in the defense mechanism of plants against microbial pathogens.

Screening for Y-derived sex determining gene SRY in 40 patients with Turner syndrome.

In Turner patients, the presence of a Y chromosome or derivative Y is correlated with the risk of gonadoblastoma induction. "Marker" chromosomes originating from Y, may not show characteristic fluorescence and then be very difficult to identify by conventional cytogenetic techniques, although they still predispose the patients to gonadal tumors. Using polymerase chain reaction of the gene from the sex-determining region of the Y chromosome, we screened 40 Turner patients (thirty seven 45X and three 45X,46XX) for the presence of Y chromosomal DNA. We were able to identify karyotypically unrecognized Y chromosome material in 1 patient out of the 40 studied. In this patient mild clinical and biological hyperandrogenism was observed. Reliability of our technique was ascertained by the detection of the expected 648 base pairs amplified DNA fragment in all normal male controls as well as in 3 Turner patients with confirmed 45X,46XY mosaicism. Despite the low frequency of unrecognized Y chromosome material (1 case over 40 in our experience), our data suggest that polymerase chain reaction of the gene from the sex-determining region of the Y chromosome is worthy of being performed in Turner patients considering the potential risk of the presence of a Y chromosome.

Management of hyperandrogenism in adolescent girls.

Hyperandrogenism in adolescent girls can be a troubling problem because of the difficulty in establishing a diagnosis and in prescribing appropriate therapy. Androgen excess in adolescent patients encompasses a spectrum of clinical presentations, including acne, hirsutism, oligomenorrhea, amenorrhea, virilism, and ovarian cysts. Androgen excess is a clinical and chemical feature of idiopathic hirsutism, late-onset forms of congenital adrenal hyperplasia, and polycystic ovarian disease; in some cases, functional hyperandrogenism is discussed. We recommend screening for hyperandrogenism by measuring blood levels of testosterone, dehydroepiandrosterone sulfate, and delta 4-androstenedione, while others propose a first dexamethasone suppression test for evaluation of free testosterone, dehydroepiandrosterone sulfate, and cortisol. Treatment will be chosen according to particular symptoms such as acne, hirsutism, obesity, or oligomenorrhea.

Retroperitoneal fibrosis in two patients with Parkinson's disease treated with bromocriptine.

Retroperitoneal fibrosis has been observed in two patients with Parkinson's disease treated with bromocriptine. The patients complained of abdominal or lower back pain and presented with various degrees of renal insufficiency, with anuria in one. Laboratory evaluation furthermore showed an increased sedimentation rate and inflammatory anemia. Computerized tomography disclosed marked retroperitoneal thickening, and biopsy was performed in one patient. The symptoms appeared eighteen months and five years after treatment was started, at doses of 20 and 22.5 mg of bromocriptine daily. The medication was discontinued in both patients and steroid therapy was initiated, with resolution of all clinical, biological and radiological evidence of disease. This potential but rare complication of a widely prescribed drug warrants monitoring of renal function and sedimentation rate in patients undergoing bromocriptine treatment.