A set of standard clinical chemistry and hematology parameters are usually measured during clinical studies. The major outcome of these standard tests is to control that the drug investigated does not lead to pathophysiological changes in respective organs or blood. In some cases based on scientific rationale such tests may not be needed.In this paper we report on a standard set of clinical chemistry and hematology laboratory parameters measured before and after treatment in three different immunotherapy studies, representing different routes of administration and different formulations.Thirteen hematological laboratory parameters and eight clinical chemistry parameters were evaluated from three double-blind, placebo-controlled, randomized, multi-centre, phase III studies. The three studies include one with sublingual immunotherapy (n = 185), one subcutaneous immunotherapy trial with an aluminium hydroxide-adsorbed recombinant hypoallergenic Bet v1-FV (n = 211) and one with pre-seasonal subcutaneous immunotherapy with a 6-grass pollen allergoid (n = 154).Allergen specific immunotherapy with both administration forms and formulations respectively did not show any influence on any of the 21 laboratory parameters analyzed. Few patients had a change in laboratory parameters from within normal range at baseline to either below or above at end-of-treatment. No differences between active and placebo were seen with respect to number of patients with such a change.This study with different preparations and routes of application indicates that the value of repeated measurements of standard clinical chemistry and hematology parameters during allergen immunotherapy should be discussed further. As a routine analysis for evaluation of safety in clinical development programs for new drugs, a set of standard clinical chemistry and hematology parameters are measured. The major outcome of these standard tests is to control that the drug investigated does not lead to pathophysiological changes in respective organs or blood. Guidelines from EMA on safety pharmacology studies discuss such a pharmacology core battery for investigation of vital functions and that in some cases based on scientific rationale such tests may not be needed . In the Allergen specific immunotherapy is known to be an efficient treatment for respiratory allergic diseases and based on clinical investigations also shown to have a good safety profile including only potential allergic side effects in patients already allergic to the allergen they are treated with . In receIn this paper we report on a standard set of clinical chemistry and hematology laboratory tests measured before and after treatment in three different immunotherapy studies, representing different routes of administration and different formulations.Thirteen hematological laboratory parameters and eight clinical chemistry parameters Table  were evaThe first study was performed with sublingual immunotherapy (SLIT) of the high dose grass pollen preparation (ALLERSLIT® forte) (SLIT 6-grass study) and included 185 patients . Mean agAll patients had a history of IgE-mediated seasonal allergic rhinitis/conjunctivitis with or without asthma (GINA stage I and II) caused by grass pollen (grass studies) or birch pollen (birch study), positive skin prick test result to grass pollen extract (grass studies) or birch pollen extract (birch study), and positive conjunctival provocation test with grass pollen allergens (grass studies) or birch pollen allergens (birch study). Only patients with moderate to severe allergic symptoms to grass or birch pollen were included in the clinical trials. Patients were excluded if they previously had undergone grass or birch pollen immunotherapy or suffered from other seasonal allergies in the same period as the relevant grass or birch pollen, or had a history of cardiovascular or other immunological or medically relevant diseases.Holcus lanatus, Dactylis glomerata, Lolium perenne, Phleum pratense, Poa pratensis, and Festuca elatior) or placebo from January 2004 until end of grass pollen season in 2005. The group 5 allergen content of the active maintenance dose corresponded to 40 μg. Patients in the SCIT rBirch study were treated with subcutaneous injections of recombinant hypoallergenic variant of the major birch pollen allergen  or placebo from October 2004 until end of birch pollen season in 2006. Treatment of patients in the SCIT 6-grass study included pre-seasonal weekly injections with either 6-grass pollen  allergoid or placebo until the expected onset of the grass pollen season 2001 and 2002.After up-dosing patients in the SLIT 6-grass study were treated daily with high-dose sublingual 6-grass pollen preparation ; SLIT: Sublingual immunotherapy; SLIT 6-grass study: Sublingual immunotherapy study with a high dose 6-grass pollen preparation.All authors are employees of Allergopharma GmbH & Co. KG. The authors declare that they have no competing interests.DH, VG and AN were involved in the design of the studies, data interpretation and drafting, revising and final approval of the manuscript. All authors read and approved the final manuscript.A list of all participating ethics committees.Click here for file


Respiratory and cardiac motion in PET/MR imaging leads to reduced quantitative and qualitative image accuracy. Correction methodologies involve the use of double gated acquisitions which lead to low signal-to-noise ratio (SNR) and to issues concerning the combination of cardiac and respiratory frames. The objective of this work is to use a generalized reconstruction by inversion of coupled systems (GRICS) approach, previously used for PET/MR respiratory motion correction, combined with a cardiac phase signal and a reconstruction incorporated PET motion correction approach in order to reconstruct motion free images from dual gated PET acquisitions. The GRICS method consists of formulating parallel MRI in the presence of patient motion as a coupled inverse problem. Its resolution, using a fixed-point method, allows the reconstructed image to be improved using a motion model constructed from the raw MR data and two respiratory belts. GRICS obtained respiratory displacements are interpolated using the cardiac phase derived from an ECG to model simultaneous cardiac and respiratory motion. Three different volunteer datasets (4DMR acquisitions) were used for evaluation. GATE was used to simulate 4DPET datasets corresponding to the acquired 4DMR images. Simulated data were subsequently binned using 16 cardiac phases (M1) vs diastole only (M2), in combination with 8 respiratory amplitude gates. Respiratory and cardiac motion corrected PET images using either M1 or M2 were compared to respiratory only corrected images and evaluated in terms of SNR and contrast improvement. Significant visual improvements were obtained when correcting simultaneously for respiratory and cardiac motion (using 16 cardiac phase or diastole only) compared to respiratory motion only compensation. Results were confirmed by an associated increased SNR and contrast. Results indicate that using GRICS is an efficient tool for respiratory and cardiac motion correction in dual gated PET/MR imaging.


MicroRNAs have emerged in recent years as important regulators of cell function in both normal and diseased cells. MiRNAs coordinately regulate large suites of target genes by mRNA degradation and/or translational inhibition. The mRNA target specificities of miRNAs in animals are primarily encoded within a 7 nt “seed region” mapping to positions 2–8 at the molecule's 5′ end. We here combine computational analyses with experimental studies to explore the functional significance of sequence variation within the seed region of human miRNAs. The results indicate that a substitution of even a single nucleotide within the seed region changes the spectrum of mRNA targets by >50%. The high functional cost of even single nucleotide changes within seed regions is consistent with their high sequence conservation among miRNA families both within and between species and suggests processes that may underlie the evolution of miRNA regulatory control. RNA-induced silencing complex (RISC) recognize their regulatory targets by Watson-Crick base pairing to compatible sequences  in target mRNAs.MicroRNAs (miRNAs) are small 20–22 nucleotide (nt) RNA molecules that play important regulatory roles in cell function It is estimated that there are >1000 sequentially distinct miRNAs in the human genome, each being present in a few to hundreds of copies To determine the mRNA targets of the 249 conserved miRNAs, we utilized three online target prediction programs, miRanda-mirSVR We determined the distance between two sequences by calculating the Hamming distance 2. The transfection protocol was as described previously HEY RNA was extracted from transfected cells using the RNeasy Mini RNA isolation kit . Microarray experiments were performed as previously described http://www.ncbi.nlm.nih.gov) SuperSeries number GSE56973.To determine differentially expressed genes in triplicates of experimental miRNA and negative control treated cells, the following procedure was followed. Quality control was first assessed using all raw CEL files as implemented in Array Analysis Homo sapiens genes were selected on BioMart and filtered to remove the genes with no mouse orthologs. The output file included the mouse orthologs for all the resulting genes. These genes were then used for our comparison of miR-429 and miR-200b predictions across human and mouse species.Orthologous genes in human and mouse were identified using the BioMart data-mining tool The functional consequence or “cost” of seed region nucleotide changes involves the loss of regulatory control over previously targeted mRNAs and/or the acquisition of novel regulatory control over previously untargeted mRNAs. To systematically explore this phenomenon computationally, we first determined the number of nucleotide changes needed to transform one seed region into another (Hamming distance) for each of the 249 miRNAs analyzed in this study. We then calculated the percent overlap (cosine similarity) of predicted targets for all pairs of miRNAs having identical seeds. For example, the percent target gene overlap for miR-25 and miR-32 (both having the seed sequence: 5′AUUGCAC) predicted by miRanda-mirSVR is 81% . The 19%We next independently computed the average percent overlap of predicted mRNA targets for pairs of miRNAs having seeds that differ by 1 to 7 nucleotides. The results  indicatein vivo because they ignore the myriad of indirect regulatory effects induced by miRNAs While informative in their own right, functional predictions based on target prediction algorithms alone are often inaccurate 2 = 1511; p<0.0001) and consistent with the prediction that a substantial functional cost is associated with even a single nucleotide change within miRNA seed regions. Differences in overlap between the miR-429 vs M12 and miR-429 vs M14 comparisons were not found to differ significantly  indicating that, in this experimental context, position of the single nucleotide change is not significant with respect to functional cost.As mentioned above, the functional cost associated with nucleotide changes within seed regions is reflective of the loss of regulatory control over previously targeted mRNAs and/or the acquisition of novel regulatory control over previously untargeted mRNAs. We experimentally estimated these parameters by comparing all significantly differentially expressed genes in cells transfected by miRNAs with seeds differing by 0 (miR-429 vs miR-429), 1 (miR-429 vs M12 and miR-429 vs M14) or 5 (miR-429 vs M5) nucleotides. Presented in 2 = 1535; p<0.0001) but not significantly different from the changes induced by miRNAs with only a single nucleotide difference from miR-429 .Changes in the percent overlap of significantly differentially expressed genes between cells transfected by miR-429 vs those transfected by the miRNA differing at 5 nucleotide positions within the seed region  were alsCollectively, the above results indicate that even a single nucleotide substitution within the seed regions of miRNAs is associated with substantial functional cost and suggests an evolutionary model whereby strong stabilizing selection is maintaining rigid conservation of miRNA seed sequences both within and between species. Individual target genes, on the other hand, may acquire and/or lose miRNA regulatory control(s) through even single nucleotide substitutions in miRNA target sequences complimentary to miRNA seeds  . Any funAs an initial test of this prediction, we selected two miRNAs (miR-429 and miR-200b) that have identical seed regions in both humans and mice . We emplCollectively, our findings support an evolutionary model whereby miRNAs initially evolve to regulate large suites of target genes. Thereafter, the sequential integrity of miRNA seed regions is maintained by strong stabilizing selection due to the high functional cost of even a single nucleotide mutation within miRNAs. In contrast, nucleotide mutations in the target sequences of individual genes, being, on average, of substantially lower functional cost, allow for a relatively rapid repositioning of miRNA-target gene associations. Indeed, a variety of scenarios might arise to buffer the possible negative effects of target sequence mutations in regulated genes. For example, duplication of specific target sequences within regulated genes could serve to mask the impact of the sudden loss of existing miRNA regulatory controls while still permitting genes to explore the potential adaptive benefits of acquiring new miRNA regulatory controls.S1 FigureOne nucleotide difference or 7 nucleotide differences in the seed regions of miRNAs is predicted to be associated with equivalent levels of change in regulated target genes. (a) miRNAs with identical seeds, miR-195 and miR-16, are predicted to share 91% of their target genes; (b) miRNAs with a single nucleotide change in their seed regions, miR-195 and miR-29a, are predicted to share only 21% of their target genes; (c) miRNAs with no sequence similarity in their seed regions, miR-195 and miR-205, are predicted to share only 18% of their target genes. These results are consistent with the hypothesis that as little as a single nucleotide difference within miRNA seed regions has a major effect on miRNA regulatory control.(PDF)Click here for additional data file.S2 FigureDistribution of percent overlap of miRanda-mirSVR predicted targets of miRNAs having 0 through 7 seed mismatches. Insets show distribution according to two other popular prediction algorithms: a) TargetScan, and b) PicTar. The results are uniformly consistent with the prediction that even a single nucleotide mismatch within miRNA seed regions results in a large change in targeted mRNAs.(PDF)Click here for additional data file.S1 TableTarget overlap for miRNAs with identical seeds. Predicted (miRanda-mirSVR) overlap (cosine similarity) in target genes for all pairs of miRNAs with identical seed regions.(XLSX)Click here for additional data file.S2 TableTarget overlap for miRNAs with non-identical seeds. Predicted (miRanda-mirSVR) overlap (cosine similarity) in target genes for all pairs of miRNAs with non-identical seed regions.(XLSX)Click here for additional data file.S3 TableFold-change for all (5229) significantly differentially expressed genes after ectopic expression of miR-429 in HEY cells.(XLS)Click here for additional data file.S4 TableFold-change for all  significantly differentially expressed genes after ectopic expression of M12 in HEY cells.(XLS)Click here for additional data file.S5 TableFold-change for all  significantly differentially expressed genes after ectopic expression of M14 in HEY cells.(XLS)Click here for additional data file.S6 TableFold-change for all  significantly differentially expressed genes after ectopic expression of M5 in HEY cells.(XLS)Click here for additional data file.


Plakin repeat domains mediate the interactions of these proteins with the cell cytoskeleton and are critical for the maintenance of tissue integrity. Despite their biological importance, no solution state resonance assignments are available for any homologue. Here we report the essentially complete  Envoplakin is a member of the plakin family of cytolinkers. Plakin proteins connect elements of the cell cytoskeleton to each other and to junctional complexes at the cell membrane. The plakin proteins play a vital role in the maintenance of tissue integrity, particularly in tissues such as the heart and skin that are subjected to high levels of mechanical stress  and resuspended in phosphate buffered saline with complete EDTA-free protease inhibitors (Roche). The cells were lysed using an EmulsiFlex-C3 (Avestin) and the lysate cleared by centrifugation . The envoplakin PRD was purified from the supernatant by nickel affinity chromatography using HisTrap HP columns (GE Life Sciences). The poly-His tag was cleaved using Tobacco Etch Virus protease, leaving 8 exogenous residues. The PRD was further purified by size exclusion chromatography using a Superdex-75 column (GE Life Sciences).A construct comprising the complete human envoplakin PRD module (residues 1822–2014) was expressed with a cleavable N-terminal His-tag using the pProEx HTc vector (Life Technologies) in BL21 (DE3) NMR experiments were performed at 298 K on Agilent NMR spectrometers equipped with cryogenic Z-axis pulse field gradient probes. Backbone assignments were made using BEST versions of the HNCA, HNCACB, HNCOCA, HNCO and HNCACO experiments  under accession number 26642.The own Fig.  indicateown Fig.  and the


Mucinous cystic neoplasm (MCN) occurs predominantly in women (>95%) with a mean age of approximately 45 years and most commonly is located in the pancreatic body or tail. The mass is lined by mucin-producing columnar epithelium with a fibrous ovarian-type stroma. The epithelial lining can contain various degrees of atypia, ranging from adenoma to invasive carcinoma. The CT and MR appearance is that of a thick walled cystic mass with septa and/or mural nodules. The contour of the mass is smooth, and the wall or septa may contain calcification. Endoscopic ultrasound with fine needle aspiration of the cyst fluid to assess CEA level may be helpful in distinguishing MCN from serous cystadenoma. CEA <5 ng/mL favors serous cystadenoma, whereas CEA >192 ng/mL favors MCN, with an accuracy of approximately 80% [Serous cystadenoma (SCA) also occurs predominantly in women (approximately 75%), but the mean age is older (mid 50s to early 60s). It is lined by glycogen-rich cuboidal epithelium and is considered a benign neoplasm, although rare cases of malignant SCA have been reported. The typical appearance is that of a lobulated mass consisting of numerous tiny cysts which give it a honeycomb appearance. Larger lesions may contain a central stellate scar and calcifications. Oligocystic or macrocystic SCA is an uncommon variant comprised of a small number of larger cysts. Distinction between macrocystic SCA and MCN can be made based on the lobulated contour of SCA, its multiple clustered cyst configuration and homogeneity of each locule on T1 weighted MR images [R images . SurgicaR images .Solid pseudopapillary neoplasm (SPN) is a rare low-grade malignancy that predominantly affects younger women (>80%), with a median age 30-38 years [38 years ,6. It isCystic neuroendocrine neoplasm of the pancreas most commonly occurs in patients with multiple endocrine neoplasia type I and usually is nonfunctional [nctional . It genenctional .


TN usually leads to paroxysms of short lasting but very severe pain. Between the attacks the patient is usually asymptomatic, but a constant dull background pain may persist. Carbamazepine is currently the drug of first choice in the treatment of TN. It is efficient in 70-80% of patients but often associated with severe adverse effects such as drowsiness, confusion, nausea and ataxia, which may require discontinuation of medication. Surgical interventions may not be suitable for all patients and waiting for the procedure can be agonizing. Therefore different non-invasive treatment options are indispensable.To investigate the efficacy of transcranial direct current stimulation (tDCS) of the primary motor cortex on pain and trigeminal nociceptive processing in subjects with classical trigeminal neuralgia (TN).Seventeen subjects with TN were recruited in the study. Patients stimulated daily for 20 minutes over two weeks using anodal (1mA) or sham tDCS in a randomized cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS). VRS and attack frequency were assessed daily for one month before and after tDCS using an individual patient diary. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead (V1) before and after tDCS. All patients gave written informed consent prior to study inclusion. The study was approved by the Ethics committee of University of Duisburg-Essen medical faculty.Anodal tDCS reduced pain intensity more effectively than sham stimulation after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported. Patients with concomitant chronic background pain do not seem to benefit from tDCS as described previously for medical therapy and surgical intervention.Daily anodal tDCS over two weeks ameliorates trigeminal pain in TN. It may become a valuable treatment option for patients unresponsive to conventional medical treatment or on wait for surgical procedures. International, multicenter, randomized controlled trials are needed with higher patient numbers before a definite recommendation can be proposed.No conflict of interest.


Antibody engineering allows proper design of improved properties in antibody products such as a high binding affinity, stable biophysical properties and low immunogenicity. Besides these obvious features improved by elegant design the primary amino acid sequence also has tremendous effects on the performance of the expression host itself influencing cell culture parameters including specific productivities and growth rates therefore having major impact on the finally obtained antibody expression titers . By undeMany different antibody variants were expressed in our group in different projects based on various isotypes. For several antibody variable regions we could observe a direct correlation of advantageous cell performance and a high degree of similarity to the closest human germline sequence of the respective mature antibody leading to higher specific productivities. However, the fundamental principles of these consistent observations and the correlation of cell behavior and biophysical product properties remain quite elusive. Therefore, in this project we aim to set the proper foundations to investigate the generalization of a concept to improve cell performance and antibody expression based on the primary sequence at a high germinality degree Figure . To haveAll cell lines  were grown under serum- and protein-free conditions in chemically defined media in suspension using shaker flasks. Transfections were performed with the cationic 25kDa linear polymer polyethylenimine (PEI). Stable subclones were either generated by limited dilution subcloning or fluorescence-activated cell sorting (FACS).Germline antibody sequences were identified by the IgBlast program. Variable antibody sequences were synthesized and cloned into vectors containing leader and constant antibody regions.For recombinase-mediated cassette exchange a CMV (for DUKX-B11) or CAGGS (for CHO-K1) promoter was placed 5' upstream of the first flippase recognition target site to establish a promoter trap in the parental RMCE-cassette. A selection/reporter marker was placed in-between two heterospecific FRT sites harboring a gfp/thymidine-kinase/neomycin-phosphotransferase fusion protein. Antibody producing cells were developed after recombination with the reporter marker by negative selection with ganciclovir. Antibody product was purified by protein A chromatography.The observed expression levels in cell cultures are influenced by many different parameters that should be controlled for a valid comparison of different antibody variable sequences. Besides different host cell lines and media formulations our group also has standardized fermentation process protocols and biophysical analytical tools for in-depth investigations of possible correlation between cell culture performance, product quality attributes and expression levels. Recently, we also engineered a CHO DUKX-B11 host cell line suitable for recombinase-mediated cassette exchange (RMCE)  to contrAn improved RMCE host cell line and an antibody panel consisting of versatile variable regions including mature antibodies and respective germline antibody sequences were constructed for in-depth analysis of cell culture parameters and biophysical properties evoked by different degrees of germinality. By understanding the underlying principles it should be possible to improve antibody cell culture processes and biophysical features by means of proper antibody engineering to optimize the primary antibody sequence.


Calciphylaxis following acute renal failure is rare.We report A 57-year-old male with an acute renal failure associated with necrotizing fasciitis. We also review the cases of calciphylaxis due to acute renal disorder further.It should be kept in mind that calciphylaxis is observed in patient with not only chronic renal disease but also acute renal failure. Calciphylaxis is a disease of cutaneous vessel calcification-induced skin ulceration Hayashi . AlthougA 57-year-old male with an acute renal failure associated with necrotizing fasciitis underwent hemodialysis. He had no history of diabetes mellitus or heavy smoking. Six weeks after the hemodialysis, he noticed painful skin ulcers on both of his legs, which gradually enlarged without any rubbing or other outer physical stimuli. Physical examination revealed a skin ulcer covered with black-yellowish necrotic tissue Fig. a. DorsalAlthough almost all cases with calciphylaxis have been described in patients with end-stage renal disease on hemodialysis, this patient exhibited calciphylaxis following hemodialysis due to acute renal failure. To clarify the detail characteristics, we review the cases of calciphylaxis associated with acute renal failure. There have been three reported cases including our case Table  Honda e. All casIt should be kept in mind that calciphylaxis is observed in patient with not only chronic renal disease but also acute renal failure. Because of limited number of cases, further investigation is necessary to clarify the detail mechanism of calciphylaxis due to acute renal failure.


Toxoplasma gondii. Toxoplasmosis is considered one of the most common cerebral opportunistic infections in HIV-AIDS patients. It develops when CD4 count falls below 100 cells/cmm, either from acute exposure to the parasite or from reactivation of latent infection. These patients may also develop extra-cerebral toxoplasmosis such as ocular toxoplasmosis and pulmonary diseases. Another clinical manifestation described in HIV-infected patients is disseminated toxoplasmosis which consists of fever, pulmonary infiltrates and sepsis-like syndrome.Toxoplasmosis is a disease caused by the intracellular parasite T. gondii, CMV and fungal infection. We noticed also an extensive ulcerated esophagitis of HSV and fungal etiology.We present a case of a 22 years old female patient diagnosed with HIV since her childhood. Over the years she was uncompliant to combined antiretroviral therapy (cART). After 16 years from her HIV diagnosis she presented an acute hepatitis type C with severe prolonged evolution, from which she slowly recover after a period of 3 months. After discharge she was well for about one month but came back with left hemiparesis difficulties in speech and visual disturbances. Also during this last hospitalization she presented a severe bronchopneumonia. After 20 days of hospitalization she died. Postmortem histopathological examinations revealed a disseminated toxoplasmosis involving multiple organ systems: central nervous system, lung, liver, spleen and lymph nodes. Lung examinations revealed bronchopneumonia due to multiple opportunistic coinfections with In immunosuppressed patients disseminated toxoplasmosis has a polymorphic clinical presentation requiring a more attentive investigation because it may hide also an involvement with other opportunistic infections. The syndrome of disseminated toxoplasmosis is affecting more than two organs and it is highly lethal in HIV positive patients.


While cutaneous metastases are already extremely rare in primary metastatic prostatic adenocarcinoma, cutaneous manifestations in recurrent prostate cancer have rarely been described prior to this report. Here we present the case report of a 93-year-old male who underwent radical prostatectomy but eventually suffered from a previously undescribed recurrence of prostatic adenocarcinoma with distant cutaneous metastases to proximal right lower leg. Adenocarcinoma of the prostate is the most commonly diagnosed nondermatological malignancy among men and a leading cause of cancer-related mortality, second only to lung cancer. Despite the high incidence and prevalence of prostate cancer in society, distant cutaneous metastases tend to occur exceptionally infrequently—reported at <0.1% in primary disease –4. Of noA 93-year-old man presented with gross hematuria and a red, translucent papule on his proximal right lower leg . Twenty Next to early-stage primary dermatological neoplasms, prostate cancer remains one of the most curable malignancies, with encouraging recurrence-free five-year survival rates greater than 80% . Most paCutaneous manifestations are associated with a poor prognosis because of the presumed systemic involvement required to develop such overt metastatic disease. The mean survival time after diagnosis of cutaneous metastasis has been calculated at 7 months . Because


Segmentectomy is an anatomic sublobar resection that has recently been introduced for small lesions in cases of lung cancer.In completion lobectomy after segmentectomy, pleural adhesion in the hilar vessels and inter-segmental plane makes the procedure most difficult. Preventing adhesion could reduce intraoperative bleeding and operation time in cases of reoperation.Here, we present a case of right S9+10 segmentectomy followed by completion lobectomy for unanticipated nodal metastasis of cT1N0/pN1 lung cancer, in which pleural adhesion was prevented by coating with fibrin glue.We describe the case of a 54-year-old man who underwent completion lobectomy for unanticipated hilar nodal metastasis reported on postoperative pathologic examination 1 month after right S8+9 segmentectomy for clinical T1N0 lung cancer. In the initial surgery, we used electrocautery without a stapler to divide the inter-segmental plane. The entire dissected inter-segmental plane was covered with absorbable mesh and fibrin glue. At re-thoracotomy, pleural adhesion at the inter-segmental plane was never observed although there were adhesions at parietal pleura not covered with fibrin glue.Covering the inter-segmental plane with fibrin glue may be useful not only for preventing air leakage but also for preventing pleural adhesion.Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.


Isolated thoracic spinous process fractures involving multiple adjacent vertebral segments are a rare occurrence in the setting of high-energy trauma. These findings should prompt further investigation to exclude other concomitant osseous or ligamentous injuries. Evaluation by computed tomography is often most useful to detect these fractures. Proper treatment of extensive multilevel injury is poorly defined in the literature. In our experience, conservative management consisting of initial bracing with graduated lifting restrictions has produced excellent functional results. The term “Clay-Shoveler's fracture” was originally coined in 1940 to describe isolated spinous process fractures occurring from C6-T3 in Western Australian laborers –6. ThereA 53-year-old male was involved in a motorcycle collision at a speed of approximately 40 mph. Physical exam was significant for right-sided paraspinal tenderness in the thoracic region. He had no neurologic deficits. Computed tomography (CT) revealed thoracic spinous process fractures within T5–T10 without evidence of vertebral body injury, extension into the lamina, or ligamentous compromise . He alsoA 53-year-old man without a helmet lost control of his motorcycle and collided with a guardrail. He had loss of consciousness and an initial Glasgow coma scale score of 12. Physical exam revealed no gross abnormalities of the spine; however he expressed significant left-sided paraspinal tenderness in the thoracic region. CT of his spine revealed isolated fractures of the thoracic spinous processes within T6–T10 without any other evidence of spine pathology . He alsoIsolated thoracic spinous process fractures involving five or more contiguous vertebrae are rarely encountered in the orthopaedic literature. These fractures often occur in conjunction with other bony or soft tissue injuries of the vertebral column. The two aforementioned cases almost double the reported literature on this specific fracture pattern. Although this pattern of injury has been referred to elsewhere as “Clay-Shoveler's fracture,” it should be considered a different entity based on the energy mechanism, level, and extent of contiguous segment involvement. Meyer et al.  describeOther authors have recently reported cases of extensive multilevel spinous process fractures involving the cervicothoracic junction , 10. HowIsolated thoracic spinous process fractures are stable injuries, which are routinely treated with conservative therapy. Even in the setting of multilevel contiguous fractures, excellent functional outcomes are commonplace with nonoperative therapy. Conservative treatment with a TLSO brace for 6 weeks with graduated lifting restrictions for up to 10 weeks has produced great results in our experience, with both patients going on to pain-free full recovery. Persistent and focal pain over the spinous processes beyond this time period should raise concern for a symptomatic pseudoarthrosis. It is well documented that spinous process fractures infrequently achieve osseous union ; howeverIsolated thoracic spinous process fractures in the setting of high-energy trauma are a rare occurrence. Involvement of five or more contiguous thoracic vertebral segments has been reported only three times previously in the literature , 5, 7. I


NK cells contribute to melanoma cell recognition and anti-tumor immunity, which is traditionally analyzed using human peripheral blood NK cells. An important checkpoint in the progression of malignant melanoma is the metastasis to lymph nodes.To investigate the role of lymph node NK cells in disease progression, we analyzed frequency, phenotype and functions of NK cells purified from either tumor infiltrated lymph nodes or tumor-free ipsilateral lymph nodes of the same patients. Lymph node NK cells were compared to peripheral blood NK cells from either melanoma patients or healthy donors.dimCD57+CD69+CCR7+KIR+ NK cells in tumor infiltrated lymph nodes. This phenotype corresponds to a recently described fully mature and highly cytotoxic NK cell population, and indeed we found that these lymph node NK cells displayed robust anti-tumor activity against autologous melanoma cells. The NK cells trafficking from periphery to the tumor draining lymph nodes have been investigated and the chemokines pattern identified. Moreover, the presence of a high proportion of KIR+CD57+CD56dim in the infiltrated lymph nodes was associated with an improved patients’ survival.The data showed an expansion of CD56Our data suggest that NK cells from tumor infiltrated lymph nodes are attractive candidates to improve current NK cell-based immunotherapy of melanoma.


While current breast cancer staging includes lymph node involvement as a key indicator of prognosis, little is known about how healthy tissue surrounding the immediate tumor microenvironment contributes to the loco-regional spread of disease. Previous studies of the role of the immune microenvironment in breast cancer have focused on the study of intratumoral T cells, reporting that increased intratumoral CD8+ T cell proportions with decreased CD4+ T cell proportions are associated with lymph node metastasis and rapid tumor progression. We hypothesized that T cells within the unaffected breast tissue  near the tumor (2-5 cm away from the tumor margin) may influence the local/regional spread of tumor cells. Since the amount of tissue available for study from the excision of primary tumors is limited, we utilized a previously established three-dimensional explant method to expand resident T cells from fresh breast cancer and healthy-adjacent breast tissue to investigate their phenotypic and functional qualities. We compared tissues from patients with LN metastasis (n = 8) and those without LN involvement (n = 7). We defined the surface phenotype of T cells derived from breast cancer and healthy-adjacent tissue using multiparameter flow cytometry. We found that healthy-adjacent tissue from patients with LN metastases exhibited a 1.6 fold lower percentage of CD4 T cells (p < 0.01) and 3.7 fold higher percentage of CD8 T cells (p < 0.05) than patients with no LN involvement. In contrast, we did not find any statistically significant differences in the number of intratumoral CD4 and CD8 T cells in patients with LN metastases versus those with no LN involvement. We hypothesized that qualitative T cell cytokine response from the surrounding healthy adjacent tissue may also be associated with LN metastases. Our preliminary data from the study of breast cancer patients (n = 6) showed some trends of increased Th2 cytokine and decreased pro-inflammatory cytokine associated with nodal metastases. These data suggest that the tissue extending beyond the tumor microenvironment  may contribute to immune surveillance and regional metastases. While this study size is small, it demonstrates the feasibility of using the explant method to interrogate healthy-appearing tumor adjacent tissue to investigate the surrounding breast tissue environment. Our preliminary findings also indicate the potential relevance of investigating the role of T cells in tumor adjacent healthy-appearing breast tissue to provide tumor immune surveillance. Further analysis of the T cells present in healthy adjacent breast tissue is warranted.Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.


Combining focused ultrasound (FUS) with real time MRI guidance and monitoring enables a new non-invasive treatment of brain disorders. In this technique multisource ultrasound waves are focused at a single point raising the temperature gradually until ablation occurs. Lesions as small as 2-4 mm can be made, without impact on surrounding tissue or remote brain tissue.Our aim was to assess MR guided focused ultrasound (MRgFUS) as a new non-invasive surgical tool for treating essential and parkinsonian tremor by thalamotomy of the ventral-intermediate nucleus.Eight patients with severe medically refractory tremor, 4 essential tremor and 4 with Parkinsonian tremor, underwent unilateral ventral-intermediate nucleus thalamotomy using MRgFUS. Following the preoperative planning using 3D CT and 3D 3T MRI, patients lay in the MRI scanner while awake with their head immobilized in a stereotactic frame. The transducers helmet was mechanically positioned and a silicone membrane sealed the space between the patient’s head and the helmet.MRI scans was performed with the helmet and frame in place, the target identified and accuracy verified at low temperatures. Treatment consisted of multiple sonications at gradually increased temperatures. MRI thermal scan provided feedback on the temperature achieved and the target accuracy. Between sonications patients provided information concerning side effects and neurological examinations were performed to verify effect.Tremor stopped in the contralateral upper extremity in all patients immediately following the procedure. In two Parkinson disease patients ipsilateral rigidity was decreased as well. Immediate side effects included during sonications: vomiting (n=1), and transient forehead pain (2), transient vertigo (2) and following the procedure: scalp numbness , subjective transient gait unsteadiness  Clinical assessment of the examiner and patient changed from severe disability to no functional disability from tremor immediately following the procedure. Follow-up of up to 10 months show sustained effect. No late side effects were noted.Thalamotomy of the VIM using MRIgFUS is safe and effective in both Parkinson disease tremor and essential tremor with minimal mostly transient side effects. Large randomized studies and longer follow up are needed in order to assess safety and efficacy.


Delirium is frequent in the critically ill and is associated with long-term morbidity . CurrentTo investigate whether systemic corticosteroids increase the probability of transitioning to delirium in a mixed medical-surgical ICU population.We conducted a prospective cohort study in a 32bed mixed medical-surgical ICU. Critically ill adults who stayed in the ICU for more than 24hours, without acute neurological disorders or other conditions hampering delirium assessment were included. Systemic corticosteroid administration was measured daily. Dosage were converted in milligrams (mg) prednisone equivalents. Daily mental status was classified as 'coma', 'delirium', or an 'awake without delirium' state using a previously described algorithm based on the CAM-ICU score . The priA total of 1112 patients accounted for 9867 ICU days. The transition from being 'awake without delirium' to 'delirium' occurred 562 times (6%). On 3483 days (35%) systemic corticosteroids were administered, with a median dosage of 50 (interquartile range 25-75) mg prednisone equivalents. Administration of systemic corticosteroids was not significantly associated with the transition to delirium . Increasing dosage on days patients received corticosteroids was not associated with an increased odds of transitioning to delirium either .Our findings suggest that exposure to systemic corticosteroids is not a risk factor for the transition to delirium.


Human parvovirus B19 is considered an important trigger of aplastic crisis in patients with chronic congenital hemolytic disorders.We describe the case of a young adult known with hereditary microspherocytosis who presented with fever, marked agitation and confusion and a slight left hemiparesis. The cerebral imaging revealed multiple giant cystic Virchow-Robin spaces, but no other abnormalities. The complete blood counts showed pancytopenia and the peripheral blood smear revealed reticulocytopenia, confirming the diagnosis of aplastic crisis. Human parvovirus B19 infection was proven by the detection of serum DNA using PCR technique. After the initiation of packed red cells transfusion a favorable outcome was seen and his neurologic symptoms fully remitted.Direct invasion of human parvovirus B19 may induce both aplastic crisis and acute encephalopathy in patients with hereditary spherocytosis. Human parvovirus B19 may induce aplastic crisis but also acute encephalopathy through direct invasion, although in our case the transient neurological symptoms were rather an effect of hypoxia.


Differences in the relative abundance of dinucleotides, if any may provide important clues on host-driven evolution of viruses. We studied dinucleotide frequencies of large DNA viruses infecting vertebrates  and invertebrates . We have identified systematic depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature of large DNA viruses infecting invertebrates. Detailed investigation of this unique genomic signature suggests the existence of invertebrate host-induced pressures specifically targeting CpT(ApG) and CpG dinucleotides. The depletion of CpT dinucleotides among large DNA viruses infecting invertebrates is at least in part, explained by non-canonical DNA methylation by the infected host. Our findings highlight the role of invertebrate host-related factors in shaping virus evolution and they also provide the necessary framework for future studies on evolution, epigenetics and molecular biology of viruses infecting this group of hosts. Differences in the relative abundance of dinucleotides provide interesting insights on virus evolution. CpG dinucleotides in particular have received a lot of attention. Depletion of CpG dinucleotides among viruses has been linked to selective mutational pressure Mutational pressure at specific dinucleotides is a critical parameter for understanding evolution of viruses. CpG dinucleotides are heavily methylated (80%–90%) in vertebrate host genomes as opposed to low levels of methylation in invertebrate host genomes Codon usage bias is an important determinant of virus evolution. Both mutational pressure and translational selection may contribute to codon usage bias In this study, we investigate the differences in the relative abundance of dinucleotides, mutational pressure and codon usage bias between large DNA viruses infecting vertebrate- and invertebrate hosts. Well documented differences between the two host groups include (a) Depletion of CpG dinucleotides in the vertebrate host genomes http://www.ncbi.nlm.nih.gov/genomes/GenomesGroup.cgi?taxid=35237) or http://www.ncbi.nlm.nih.gov/nucleotide). When multiple full-length sequences were available for a virus, only one full-length sequence was used for analysis. The genomes with annotated tRNAs were excluded from analysis. A total of 193 sequences were used in this study; this includes 88 sequences of large DNA viruses infecting invertebrates  and 105 sequences of large DNA viruses infecting vertebrates   as compared to the large DNA viruses included in the study (average genome size 164 kb). In addition, viruses belonging to the family Iridoviridae and Polydnaviridae were also excluded from the study. The genomes of iridoviruses are known to encode DNA methyltransferases leading to heavy methylation of the cytosine residues of CpG dinucleotides Polydnaviridae are composed of multiple segments of DNA including wasp genes and wasp non-coding DNA The available full-length sequences of large double-stranded DNA (ds-DNA) viruses infecting vertebrates and invertebrates were retrieved from NCBI virus genome resources , the frequencies of the mononucleotides f(X) and f(Y) and the length of the genome G. In other words, pY of one strand will be equal to the frequency of dinucleotide Y′pX′ in the complementary strand, where Y′ and X′ are complementary nucleotides to Y and X respectively.The observed/expected ratios for the dinucleotide XpY [(O/E)Hence, the dinucleotide frequencies in a double-stranded sequence can be calculated using the following formula:http://bioweb.pasteur.fr/seqanal/interfaces/codonw.html) was used to determine the effective number of codon (ENC), total GC content and the nucleotide composition at the third codon position. The values of ENC range from 20–61, with a value of 20 representing maximum codon bias i.e one codon is used for one amino acid and a value of 61 represents no codon bias i.e. all the codons are equally used for each amino acid. ENC values of 35 or less are suggestive of significant codon usage bias.A freely available and widely used web tool, CodonW  was calculated by using the following formula: http://www.cbs.dtu.dk/services/FeatureExtract/). The observed/expected ratios for the CDS (XpY -CDSO/E) were calculated.The coding DNA sequences (CDS) as annotated in Genbank files were extracted using a web tool (3) was plotted against the GC content at the first and second codon positions . The GC1,2 values were plotted against GC3 values in a scatter plot.For each virus, total GC content and the frequency of nucleotides at the third (silent) codon position was calculated. In order to determine the relative effects of translational selection and mutation pressure, GC content at the third codon position  as appropriate. Box plots, scatter plots and column (bar) graphs were made using MS-Excel or using the software Graph pad. On each box, the central horizontal line represents the median, the edges represent lower (Q1) and upper quartiles (Q3). Scatter plots were used to compare two parameters. Results were considered statistically significant at a P value of <0.05.Data were analyzed using Student’s P<0.0001; Wilcoxon signed rank test) and the CpG dinucleotide was the most overrepresented dinucleotide  among large DNA viruses infecting invertebrate hosts.The relative abundance of dinucleotides among large DNA viruses infecting invertebrates and vertebrates are summarized in O/E ratios than those infecting vertebrates . Large DNA viruses infecting invertebrates had a significantly higher CpGO/E ratios than those infecting vertebrates  dinucleotides in large DNA viruses infecting invertebrates and vertebrates is shown in O/E ratios and GC content .The GC content ranged from 19–58% in large DNA viruses infecting invertebrate hosts and between 26–77% in those infecting vertebrate hosts. A positive correlation between GC content and CpG dinucleotide frequencies has been demonstrated in previous studies 3) and ENC values using ENC-GC3 plots. This relationship was then compared to the expected ENC value (ENC*) that would result if GC content primarily accounts for codon usage biases. In other words, ENC-GC3 plots will help assess the relative role of mutational pressure  and translational selection . Interestingly, the actual values of ENC for both the groups of viruses lie on, or just below the expected ENC curve  NC curve , indicatThe ENC statistic does not take into account the variation in nucleotide composition of the sequences studied 3) with GC content at non-synonymous first and second codon position   . The corO/E ratio will be lower than the CDS CpTO/E-CDS ratio. On the contrary, if translational selection were the major driving force for CpT depletion, one would expect that the depletion of CDS (CpTO/E-CDS) ratio will be more pronounced than the depletion of genome-wide CpTO/E ratio. Among viruses infecting invertebrates, the genome-wide depletion of CpT dinucleotides was more pronounced as compared to that within the CDS    is the major driving force leading to CpT(ApG) depletion and CpG excess among large DNA viruses infecting invertebrates we sought to investigate the difference between genome-wide dinucleotide O/E ratios and dinucleotide O/E ratios in the coding DNA sequence for a given dinucleotide. If CpT depletion is primarily driven by pressures other than translational selection , one would expect that the genome-wide CpTnk test) . Similarnk test) .O/E/TpCO/E ratios for the viruses studied. The CpTO/E/TpCO/E ratios were significantly lower in large DNA viruses infecting invertebrates as compared to those infecting vertebrates . There was no correlation between the relative abundance of CpT (ApG) dinucleotides and TpT(ApA) dinucleotides among large DNA viruses infecting vertebrate hosts . In addition, TpTO/E ratios was significantly higher among the large DNA viruses infecting invertebrates as compared to those infecting vertebrates  (Deamination of methylated cytosines results in C to T transitions <0.0001) .2r = 0.335; P<0.0001). However, there was no correlation between the relative abundance of CpT(ApG) and CpG dinucleotides among the large DNA viruses infecting vertebrate hosts .The loss of CpT(ApG) dinucleotides correlated with a gain in CpG dinucleotides among large DNA viruses infecting invertebrate hosts (O/E ratios were significantly lower among the large DNA viruses infecting invertebrates as compared to those infecting vertebrates (P<0.0001). The CpGO/E ratios were significantly higher among the large DNA viruses infecting invertebrates as compared to those infecting vertebrates (P<0.0001). Depletion of TpA dinucleotides was a common feature among both the groups of viruses (We investigated the relative abundance of dinucleotides among large DNA viruses infecting a wide range of invertebrates and vertebrates hosts. We found systematic CpT(ApG) depletion and CpG excess among large DNA viruses infecting invertebrate hosts . In cont viruses . AvoidanThe depletion of CpT dinucleotides and the presence of CpG excess appears to be a unique genomic signature of large DNA viruses infecting invertebrate hosts. To the best of our knowledge, neither CpT depletion nor CpG excess have been described among any group of viruses. Intrigued by this finding, we went on to investigate the underlying mechanisms that could potentially contribute to this unique genomic signature of large DNA viruses infecting invertebrates.O/E ratios and GC content O/E ratios . Despite their high CpGO/E ratios, large DNA viruses infecting invertebrates had lower GC content as compared to those infecting vertebrates . Thus, it is clear that higher CpGO/E ratios among large DNA viruses infecting invertebrates are not linked to higher GC content.Several studies have demonstrated a positive correlation between CpGAfter having demonstrated CpT depletion and CpG excess among large DNA viruses infecting invertebrates we asked the question if these differences arose because of translational selection or host-induced pressures other than translational selection.3 plot  is observed it suggests a major role for translational pressure; while a good correlation between GC3 and GC1,2 supports the role of mutational pressure  in shaping the nucleotide composition of the genome. We found significant correlation between GC3 and GC1,2 among viruses infecting invertebrate hosts  O/E ratios for CpT and CpG dinucleotides. The genome-wide depletion of CpT dinucleotides and the genome-wide over-representation of CpG dinucleotides were more pronounced as compared to that with the CDS .Taken together, these findings unambiguously support the role of genome-wide substitutions as the major driving force leading to CpT depletion and CpG excess among large DNA viruses infecting invertebrates. Our finding that genome-wide substitutions dominate translational selection of specific codons is in keeping with previous reports on other viruses Having demonstrated that host-induced pressures other than translational pressure contribute to CpT(ApG) depletion and CpG excess among large DNA viruses infecting invertebrate hosts we investigated if the TpC dinucleotide is also under a similar pressure. The TpC(GpA) dinucleotide has the same mononucleotide composition (C and T or A and G ) as CpT(ApG) dinucleotides.O/E ratios O/E ratios were significantly lower in large DNA viruses infecting invertebrates host as compared to those infecting vertebrate hosts  <0.0001) . This fiO/E/GpCO/E ratios among large DNA viruses infecting invertebrates are significantly higher than those infecting vertebrates (P = 0.01), suggesting that mechanisms linked to increasing or maintaining CpG dinucleotide content do not influence the GpC dinucleotide content. The CpT (and not TpC) and CpG (and not GpC) dinucleotides of large DNA viruses infecting the invertebrates represent unique targets for substitution, implying that the underlying invertebrate host-induced pressure is likely to be linked to methylation of 5-methylcytosine within the dinucleotides.Similarly, the CpGP<0.0001); but there was no such correlation among large DNA viruses infecting vertebrate hosts (P = 0.503). This finding suggests that deamination of 5-methylcytosine in CpT dinucleotides may, at least in part explain the depletion of CpT dinucleotides among large DNA viruses infecting invertebrates. In addition, higher TpTO/E ratios among the large DNA viruses infecting invertebrates as compared to those infecting vertebrates  between vertebrate and invertebrate hosts are well known 2r = 0.335; P<0.0001); but there was no such correlation among the large DNA viruses infecting vertebrates . The inverse correlation between the relative abundance of CpT and CpG dinucleotides among large DNA viruses infecting invertebrates is in keeping with finding from earlier studies on animal genomes An earlier study investigating dinucleotide frequencies among completely sequenced vertebrate and invertebrate animal genomes found a correlation between loss of CpG dinucleotides and the gain of CpT dinucleotides Despite major differences in genome organization, replication and host range among DNA viruses infecting invertebrates, CpT depletion and CpG excess have emerged to be the unifying theme across this group of viruses. This finding clearly links host-related factors to CpT depletion and CpG excess. Apart from the potential link between host methylation and the depletion of CpT dinucleotides, our findings do not elucidate specific host-related factors linked to CpT depletion or CpG excess. Two possible explanations are summarized below:The depletion of CpG dinucleotides has been linked to evasion of host immune response via stimulation of Toll-like receptor 9 (TLR9) by unmethylated CpG dinucleotides The complete genome sequence of most invertebrate and vertebrate hosts of viruses included in our study is currently unavailable. Nonetheless, data from studies analysing a limited number of complete and partial genomes indicate marginal CpT depletion in invertebrate hosts Apis mellifera (honeybee), a social insect, revealed that genes with a low CpG content (mean CpGO/E = 0.55) were linked to hypermethylation of germline DNA, while those with a high CpG content (mean CpGO/E = 1.5) were linked to hypomethylation of germline DNA The absence of TLR9 in invertebrates may potentially allow the maintenance of CpG dinucleotides in invertebrates DNA viruses. A study analysing the CpG content of genes in the In our study, the presence of excess CpG among large DNA viruses infecting invertebrates suggests that a mechanism to conserve CpGs against depletion of CpGs may exist in this group of hosts. Alternatively, large DNA viruses with increased CpG dinucleotide content may have a survival advantage in invertebrate hosts leading to a positive selection of these strains.Our findings shed new light on evolutionary differences between large DNA viruses infecting invertebrate hosts and those infecting vertebrate hosts. We have identified depletion of CpT(ApG) dinucleotides and over-representation of CpG dinucleotides as the unique genomic signature for large DNA viruses infecting invertebrates. Our data provides evidence that supports the existence of invertebrate host-induced pressures specifically acting on CpT(ApG) and CpG dinucleotides of the infecting large DNA viruses. We believe that our findings provide a framework to understand invertebrate host-related factors and their role in shaping virus evolution and perhaps virus pathogenesis.Figure S1Distribution pattern of CpT and CpG dinucleotides in large DNA viruses. The distribution pattern of CpT dinucleotides in viruses infecting (a) invertebrates and (b) vertebrates. The distribution pattern of CpG dinucleotides in viruses infecting (a) invertebrates and (b) vertebrates.(TIF)Click here for additional data file.Dataset S1Accession numbers of virus sequences and host type.(XLSX)Click here for additional data file.


A 59-year-old man with a history of chronic ankylosing spondylitis for many years, developed neck pain and left cervico-brachial neuralgia following a road traffic accident sustained one week before. Plain radiographs of cervical spine were initially misinterpreted. On examination, he had severe neck pain on mobilization without any neurological deficits. Delayed cervical computed tomography scan showed ossification of the anterior longitudinal ligament, calcification of the intervertebral discs and complete vertebral fusion  with transversal fracture at C5-C6 disc level  causing a luxation of the cervical spine with significant compromise in canal space (A and B). A transcranial spinal traction was performed followed by anterior decompression and stabilization via an anterolateral cervical approach. The outcome was favourable. Transverse fractures of the spine are rare in patients with ankylosing spondylitis and diagnosis should be considered following even minor trauma. These atypical unstable fractures occur because of the loss of flexibility and fragility of the osteoporotic spine. Early diagnosis for possible intervention is important because of the high mortality rate.


The following information is missing from the Acknowledgements section: The research leading to these results has partly received funding from the EU-FP7-SOCIOEC project under grant agreement No. 289192.


Measuring patterns of volatile organic compounds ('VOCs') in exhaled breath  is a novel metabolomic non-invasive approach to study molecular signatures of respiratory disease.to study whether controlled and uncontrolled asthmatic children treated with inhaled corticosteroids (ICS) can be identified according to their breathprint.VOCs were measured in thirty-three asthmatic children  who participated in the PACMAN2 study. All children were current users of ICS. Current asthma control was assessed using the Asthma Control Questionnaire. Long-term asthma control was based on reported symptoms in the four seasons preceding baseline and follow-up visit. A single vital capacity volume of exhaled air was collected upon 5 minutes of normal breathing through a three-way non-re-breathing valve with a VOC filter in a Tedlar bag. The VOCs in the breath sample were subsequently captured on Tenax GR Tubes and analyzed offline on a validated panel of four eNoses with different sensor technologies . Breathprints were analysed per eNose using principal component analyses (PCA). ROC curves and cross-validated accuracy values of significant (t-test) principal components were used to assess the accuracy of the devices to discriminate between controlled and uncontrolled patients. Additionally, the fraction of exhaled nitric oxide (FeNO) was measured with a NIOX Mino and an expiration time of 6 seconds.Two eNoses in the panel were able to discriminate current uncontrolled asthmatic children and controlled asthmatic children according to their breathprint . Three eNoses were able to identify long-term uncontrolled asthmatic children and long-term controlled asthmatic children . For both outcomes the Comon Invent, a metal oxide sensor, was most accurate in separating both groups. In contrast, FeNO was a poor marker to discriminate between controlled and uncontrolled asthmatic children .Breathprint analyses can accurately distinguish uncontrolled from controlled asthmatic children. In contrast, a single FeNO measurement cannot. These preliminary results suggest that breathprints might be able to identify distinct childhood asthma phenotypes.


Precision medicine utilising biomarkers to identify those patients likely to obtain a benefit from receiving a particular treatment has the potential to deliver benefit across multiple stakeholders. These are dependent upon having a well-defined biomarker positive population, which for continuous biomarkers such as gene or protein expression includes defining a threshold or cut-off based upon observed clinical data. To obtain the desired precision in estimating such a cut-off frequently requires larger sample sizes than typically used in early phase studies.A popular approach for investigating biomarker thresholds is the ‘minimum interaction p-value’ method . While this approach is flexible and relatively easy to implement, it operates independently of an efficacy target considered to be clinically meaningful.We propose an approach that anchors the biomarker threshold to a clinically meaningful treatment effect. p-splines are used to flexibly model the efficacy-biomarker relationship in order to identify the threshold defining a biomarker positive population meeting a pre-defined efficacy target. The significance of this population is tested through permutation. The method is placed within a hierarchical split-alpha testing structure also permitting the selection of an all-comers population.This innovative approach builds upon existing methods to define a biomarker cut-off and confirm efficacy within the same phase 3 trial. This method may lead to a viable path for more efficient clinical development programs and increased precision in threshold determination.


HGPS skin fibroblasts are characterized by multiple nuclear defects: nuclear shape abnormalities chromatin structure alterations, increased DNA damage and cell cycle alterations.Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by a LMNA gene transcription, due to the presence of a retinoic acid responsive element (L-RARE) in the LMNA promoter. Based on this knowledge, we investigated if all trans retinoic acid (ATRA) could lower progerin levels in HGPS fibroblasts. We also evaluated the effects of a combined treatment with rapamycin, a drug known to promote autophagy and reduce both farnesylated prelamin A and progerin amount.Retinoic acid may modulate We demonstrate a surprising effect of ATRA to repress Lamin A/C gene transcription and we show that the combined treatment with ATRA and rapamycin has a synergistic effect: it dramatically lowers progerin levels, restores both heterochromatin organization and nuclear shape, reduces DNA damage markers and improves cell viability. These promising results could open the way to a new therapeutic approach for HGPS.


The simulated optical response (absorption and responsivity) of Au nanoislands integrated in CdS films confirms the strong dependence of NIR sensitivity on the size and shape of Au nanoislands. The demonstration of plasmon enhanced IR sensitivity along with the cost-effective device fabrication method using CdS film enables the possibility of economical light harvesting applications which can be implemented in future technological applications.We report the use of random Au nanoislands to enhance the absorption of CdS photodetectors at wavelengths beyond its intrinsic absorption properties from visible to NIR spectrum enabling a high performance visible-NIR photodetector. The temperature dependent annealing method was employed to form random sized Au nanoparticles on CdS films. The hot electron induced NIR photo-detection shows high responsivity of ~780 mA/W for an area of ~57 μm The next generation photodetector based devices most likely, would be made up of hybrid nanostructures improving the intrinsic properties of the base material to new and interesting functionalities. CdS is one of the cost effective materials and photodetectors made from films or nanostructures of this material have been investigated extensively for their photosensing applications12et al. showed strong coupling between plasmons (hot electrons) and semiconductor facilitating additional optical functionality. Here, the incident NIR light (1500 nm) on metallic nanoantenna excites resonant plasmons and hot electrons injection takes place at the nanoantenna-semiconductor interfaceet al. have demonstrated plasmon-induced hot electron photocurrent generation in a grating based device patterned on a silicon substrate12et al. demonstrated the hot electron injection from Au tip into CdS nano rods and indicated the use of plasmon induced hot electron transfer for potential light harvesting applicationsThe present research advances on plasmonically enhanced hot electron photodetection enable materials to exhibit new optical functionalities for the wavelengths beyond their detection limit. The pioneering work of Knight IR light 00 nm on Here we show the use of random sized Au nanoantennas generating hot electrons arising due to surface plasmon resonance phenomena and upon its decay collecting at the interface of the CdS semiconductor which eventually increases the photocurrent. We use a simple straightforward annealing temperature dependent method of random Au nano islands formation on ultra-low cost effective CdS films made by chemical bath deposition technique. The rapid annealing of thin gold film on CdS yields the formation of Au nanoislands. Different annealing temperatures resulted in random nanoisland formation having different sizes and density of particles. The absorption enhancement in CdS layer due to integration of gold nanoislands has been investigated by using FDTD software. The photoresponse of these devices is studied for visible and NIR wavelengths. The fabricated devices clearly demonstrate that the photoconductivity response shows sensitivity to visible-NIR region with high responsivity (780 mA/W), reproducibility and stability.2 and CdS substrates. A thin layer of gold (Au) was sputtered coated on CdS film. The same sputtering chamber was used to anneal the Au films by increasing the temperature of the stage to 450°, 600° and 700 °C. The annealing temperature parameter was tuned to get the different sizes of Au nanoislands on CdS films and best photoconductivity results were obtained for 600 °C (FESEM image 19Iph) was calculated by subtracting the current values (Iph = Ilight − Idark). The stable and reproducible photocurrent response of the device was observed under different light illuminations . The device’s photocurrent and its dependency on the applied bias voltage for the device have been plotted in To know the photoconductive response of the CdS -Au nanoislands fabricated devices under white light illumination, we have performed current-voltage (I–V) and constant bias voltage dependent measurements . First, P) for 1064 nm has been shown in I ≈ PN) where exponent N determines the response of photocurrent to laser power density which we have found ≈ 0.86 i.e. close to unity and the sublinear increase in photocurrent was observed as we increase the power of the laser from 1.5 to 29 mW/cm2 at a constant bias voltage of 500 mV. The reason behind sublinear response could be due to the contribution in photocurrent coming from bolometeric effects and such effects have been reported in materials like carbon nanotubesThe performance of a CdS_Au nanoislands based integrated device for NIR light illumination is shown in 2), CdS and Au materials. The observed simulation results (R) can be understood through the relation of Fowler function (S) which is B is the Schottky barrier height, CF is the Fowler emission coefficient, hv is the energy of the incident photons). The CdS films with Au electrodes junction have been studied previously and their potential barrier height is reported as ~0.76 eVTo understand the optical properties of Au nanostructures formed on CdS films we have employed here FDTD (finite-difference time domain) method. The absorption profiles were calculated by modelling the glass (SiO results  show enh results  show tha2 (The best photoresponsivity of ~780 mA/W is observed for the devices (CdS-Au nanoislands) fabricated in this study at annealing conditions 600 °C and measurements were carried out on the smaller area ~57 μm2 . The inc2 . The cro2  shows th2 which is far better compared to CdS thin films investigated here and thus triggers the possibility of Au nanoislands formation on CdS nanoblets for investigating ultrafast photodetection. However our work enables the potential use of Au nanoislands_CdS devices converting incident light into electrical signals which is backbone of the many photodetecting applications. Moreover, we have also used a very simple cost effective approach using glass as a substrate for CdS film deposition. The deposition of CdS films by CBD technique is well established, economical and known for an effective ultra-cost, large area production. The optimized procedure for Au nanoislands formation on CdS films is also simple and reproducible. The simplicity, high responsivity and large area fabrication make these devices more suitable candidate for ultra-low-cost Visible-NIR photodetectors. To the best of our knowledge, integrating random Au islands in CdS films and showing broadspectral (visible to NIR) region is new approach which was not attempted previously and further can be exploited in hot electron induced light harvesting or high performance photodetector applications.In summary, the CdS _Au nanoisland based integrated devices demonstrate hot electron generation and their transfer in CdS films contributing to photocurrent detection. They possess very attractive optoelectronic properties such as very high responsivity (780 mA/W) and broadspectral photoresponse extending photodetection in CdS films from visible to NIR spectrum. The work on crystalline CdS nanobelt has shown ultrafast response time (~20 μs)The CdS films were deposited by chemical bath deposition method as described in earlier reports. The metal pads needed for the electrical connection on CdS films were sputtered coated through shadow masking procedure. The shadow masks were custom designed and made by the Tecan ltd, UK. Thin films of Au (6 nm) were also sputter coated and annealing was performed immediately after the deposition. The FESEM characterization  was performed to know the Au nanoislands size distributions. The CdS-Au nanoisland devices were mounted in the probe station setup [Cascade Microtech EPS150TRIAX with shield enclosure (EPS-ACC-SE750) and triax connections] which was further custom designed for photo conductivity and low signal measurements. All the electrical measurements were carried out by Keithley 2634B source measure unit (SMU).How to cite this article: Sharma, A. et al. Hot electron induced NIR detection in CdS films. Sci. Rep.6, 22939; doi: 10.1038/srep22939 (2016).


Transient left ventricular apical ballooning syndrome is characterized by transient akinesis of the left ventricular apex with basal wall hyperkinesis; this is also known as Takotsubo cardiomyopathy. There are three distinct contractile LV patterns described in the literature: apical, midventricular, and basal ballooning. The apical ballooning pattern is the most frequent pattern. We describe the case of a transient anterolateral left ventricular ballooning fulfilling the definition of Takotsubo cardiomyopathy except for the contractile LV pattern. The diagnosis was supported by cardiac magnetic resonance imaging and by the fact that the anterolateral ballooning resolved completely after 6 weeks. Transient left ventricular apical ballooning syndrome characterized by transient akinesis of the left ventricular apex with basal wall hyperkinesis was first described as Takotsubo-type cardiomyopathy in 1990 . The majWe report the case of a stress-induced left ventricular anterolateral ballooning in a 61-year-old female patient matching the diagnostic criteria of TTC but with a distinct pattern of ballooning/dyskinesia. The 61 year old female patient presented the day after new years eve with typical anginal chest pain at rest with radiation to the jaw. The ECG at presentation showed minimal ST-elevation (0.5 mm) in I and aVL and poor R wave progression V1–V4. Regarding cardiovascular risk factors the patient had mild hypertension and dyslipidemia (currently not treated). Troponin test was positive with normal values vor CK/CK-MB. An emergency coronary angiography was performed which revealed normal coronary arteries. The left ventricular angiogram showed anterolateral ballooning with globally preserved ejection fraction . 24 h laThe patient was diagnosed with an atypical form of takotsubo cardiomyopathy and discharged one day later with an ACE-inhibitor and a betablocker. 6 weeks later, the patient was seen as an outpatient. She was asymptomatic and LV function was completely normal on echo.Our case fulfills the current diagnostic criteria of stress-induced cardiomyopathy or takotsubo cardiomyopathy except for the contractile LV pattern . In formCardiovascular magnetic resonance (CMR) imaging is uniquely suited for the evaluation of patients with TTC. In addition to accurate visualization of regional wall motion abnormalities, it allows for precise quantification of right ventricular (RV) and LV function and the assessment of additional abnormalities . Importantly, CMR imaging also provides markers for reversible  and irreversible (necrosis/fibrosis) injury, which may be particularly important to verify TTC and exclude similar acute cardiac diseases such as myocardial infarction or myocarditis . In conclusion we suggest that TTC can present not only with the classical LV ballooning patterns  but also with segmental  ballooning, and CMR is a useful tool in the diagnosis of TTC.


Oral food inmunotherapy is a promising therapeutic aproach in patients with persistent cow's milk allergy (CMA). Although it seems that these protocols show a better outcome in patients with "milder" symptoms (i.e. non anaphylactic reactions) there are controversial results in highly sensitized subjects.We select patients with persistent CMA and severe uncontrolled anaphylactic symptoms despite a correct restrictive diet. We performed a two-day desensitization procedure at the Pediatric Critical Care Unit in our Institution. The second phase was weekly scheduled in the Outpatient clinic to reach a final cumulative dose of 250 ml of undiluted milk. Clinical and serological date were collected every six month for a five-year period.Fifteen children (2-16 y.o.) were included. All children reached the final dose of 250 ml of undiluted milk in less than ten weeks. Clinical follow-up every 6 months remained during 5 years to register all adverse reactions and possible factors involved. Serological changes were obtained every six months during the subsequent five years, including specific IgE and IgG4.Anaphylactic CMA patients may benefit from rush oral Cow's Milk immunotherapy. Clinical and serological changes have been found both at early and long-term follow-up. Several factors were involved in reactions for temporary loss of tolerance.


Early extubation post coronary artery bypass grafting does not increase perioperative morbidity and reduces the length of stay (LOS) in the ICU and in hospital . Use of A prospective analysis was performed on all patients post adult cardiac surgery from 14 May 2013 to 10 July 2013. Emergency surgical patients and those with intraoperative complications were excluded.t test was used to analyse the data. Patient demographics are presented in Table P = 0.0184) (Table A two-sample 4) Table . There wAdministering morphine prior to extubation causes significant delays in weaning from mechanical ventilation. We plan to introduce intraoperative and postoperative protocols to facilitate rapid weaning from mechanical ventilation for elective cardiac surgical patients.


Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease which commonly shows a remitting-relapsing course. Monitoring disease activity and adaptation of immune-suppressive therapy is still a challenge in clinical practice. In previous work our group has shown that members of the S100-protein family are reliable biomarkers for monitoring arthritis in JIA patients on medication and that these proteins may even predict risk of relapses in these patients. In my talk I will present novel data regarding the local release mechanism of these proteins during joint inflammation, use of serum concentrations of these S100-proteins for monitoring JIA as well as novel molecular imaging methods based on local S100-protein expression in preclinical models of inflammation and arthritis.None declared.


A 37-year-old previously healthy man presented with a localized headache and a progressive enlarging mass in the left frontal area for more than 8 months. He also reported a history of head injury in the same area sustained two years before. On physical examination, the mass (about 28 mm in diameter) was hard to pressure with freely mobile skin above the lesion in the left frontal sus-orbital region. Ophthalmologic and neurologic examinations were normal. Cranial computed tomography scan showed an osteolytic intradiploic lesion with poorly defined margins (A and B). Magnetic resonance imaging showed hyperintense lesion on T2-weighted image and hypointense on T1-weighted image with gadolinium enhancement (C). The lesion was extradural with slight brain mass effect. Surgery consisted of total resection of the bony bluish lesion (D) and cranioplasty. The postoperative course was uneventful. Histological study revealed a cavernous hemangioma of the diploe. Bone hemangioma is a vascular hemartoma: a benign tumor arising from the intrinsic vasculature of the bone, commonly seen in long bones and vertebrae. Skull cavernous hemangiomas are rare tumors for which the origin is not yet clear. We suspected that in our case head injury may have been the cause of cavernous hemangioma in the cranial vault.


Growing evidence suggests that, as long as the total lung capacity is not overcome, dynamic  is more injurious than static  lung deformation . BecauseIn eight healthy piglets we measured total hysteresis and the peak inspiratory pressure (Ppeak) while randomly increasing VT (with no PEEP) or PEEP (with fixed VT). P1 was extrapolated from the drop in airway pressure during an end-inspiratory pause . HystereP values refer to oneway repeated-measures analysis of variance.The main findings are shown in Figure Lung hysteresis increases with VT, but not with PEEP Further studies are needed to prospectively evaluate the role of lung hysteresis in the pathogenesis of ventilator-induced lung injury.


An anomalous origin of a coronary artery (AOCA) is the second most common cause of non-traumatic sudden cardiac death in young athletes. Patients with a malignant course of an AOCA of the right coronary artery only need surgical correction when myocardial ischaemia is detected. An AOCA and its malignant or benign course can be detected by coronary angiography, coronary computed tomography or cardiac magnetic resonance imaging. Detection of ischaemia can be more difficult since even a negative maximal-effort stress ECG does not exclude a potential lethal coronary anomaly. Also, there are no case series or trials showing sensitivity or specificity for any form of ischaemia detection for AOCA in the literature. Although not described previously in adults, dobutamine stress echocardiography was previously described in a paediatric population with AOCA. We are the first to describe ischaemia detection by dobutamine stress echocardiography in three adult patients with an AOCA of the right coronary artery who were subsequently referred for surgery.The online version of this article (doi: 10.1007/s12471-014-0648-3) contains supplementary material, which is available to authorized users. An anomalous origin of a coronary artery (AOCA) is the second most common cause of non-traumatic sudden cardiac death in young athletes . PatientAn AOCA and its malignant or benign course can be detected by coronary angiography (best including a right oblique view), coronary computed tomography or cardiac magnetic resonance imaging . DetectiSince normal routine exercise electrocardiography test does not exclude ischaemia in patients with AOCA, we suggest the use of dobutamine stress echocardiography in patients with AOCA.(DOCX 1493 kb)


High-grade  gliomas are undifferentiated or anaplastic, are highly infiltrating and termed as malignant. The overall prognosis and survival rate is very low. Only few highly sensitive and specific biomarkers for Glioma have been identified, but are yet to be put for routine use due to challenges in their clinical validation for early disease detection, diagnosis and monitoring to improve long-term survival of patients. The inefficacy of currently available chemotherapeutic and radio-therapeutic agents largely depends on a number of resistance mechanisms among which DNA repair plays an important role. Hence bio-molecules involved in DNA repair mechanisms will be promising biomarkers. Current status in the validation of DNA repair genes include, studying the promoter methylation of the only direct DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). MGMT is epigenetically inactivated via hypermethylation of the 5′-CpG islands located in promoter region. It is associated with prediction of successful alkylating agent therapy with temozolomide in combination with radiotherapy and also longer overall survival in patients. The silenced MGMT gene possibly enhances radiation effects by inducing radiation-mediated double stranded DNA (dsDNA) breaks and suppression of dsDNA repair pathways after radiation exposure.Post surgery excised tumor samples from 20 patients diagnosed histopathologically with high grade glioma were tested for MGMT promoter region methylation status. DNA extraction and bisulphate conversion using suitable commercially available kits (Qiagen) followed by Methylation specific PCR using specific methylated and unmethylated primers was carried out. Correlations are underway with clinical profile and treatment regimen.Hypermethylation of the promoter region was observed in about 60%, (12) samples. The other samples only demonstrated unmethylated regions.Assessment of promoter methylation of the MGMT gene helps in the therapeutic choice of the patients. It has gained importance not only as a prognostic but also as a predictive biomarker in molecular profiling of high grade gliomas.


This report illustrates an unusual case of asymptomatic late cardiac perforation by an atrial pacemaker lead into the right lung. In the present case, the lead was explanted by simple manual traction through the device pocket without any complications. A 33-year-old patient with no evidence of underlying cardiomyopathy was implanted with a dual-chamber pacemaker  Zephyr XL DR; active fixation atrial lead SJM Tendril ST 1882T/52; passive ventricular lead SJM Tendril ST 1888T/58) for symptomatic complete atrioventricular (AV) block. The implantation procedure was uneventful and usual follow-up including device interrogation and chest radiography remained normal until the 8-month follow-up visit. During this last consultation, although the patient remained totally asymptomatic, both atrial sensing and capture were lost. Chest radiography revealed a clear migration of the atrial lead into the right lung . ContrasPacemaker implantation is a very common procedure that usually carries a low risk of complications. Acute perforation of a cardiac cavity by a pacemaker lead occurs in about 1% of the patients at time of the implantation . HoweverThis case report illustrates a rare case of asymptomatic late cardiac perforation of an atrial pacemaker lead into the right lung. In such situation, simple manual lead extraction through the device pocket is worth trying and allows for avoiding an invasive surgical approach.


A 2-year-old male with Poland-Moebius syndrome was transferred from a local hospital to the Pediatric ICU at Children's Hospital of Georgia for suspected postobstructive pulmonary edema (POPE) after tonsillectomy/adenoidectomy (T&A). The patient's respiratory status ultimately declined and he developed respiratory failure. Imaging suggested pulmonary edema as well as a left-sided pneumonia. Echocardiogram showed pulmonary hypertension and airway exam via direct fiberoptic bronchoscopy revealed tracheomalacia and bronchomalacia. He developed acute respiratory distress syndrome (ARDS) and remained intubated for ten days. This case highlights the association between congenital upper body abnormalities with cranial nerve dysfunction and the development of POPE with delayed resolution of symptoms. Patients with upper body abnormalities as above are at great risk of postoperative complications and should therefore be managed in a tertiary-care facility. We present a case of postobstructive pulmonary edema after T&A in a child with Poland-Moebius syndrome. These relatively uncommon anomalies likely contributed to postoperative complications for this child including POPE and ARDS. Patients with similar upper body abnormalities should be recognized as high risk of development of postoperative complications following T&A.A 2-year-old male with Poland-Moebius syndrome had tonsillectomy/adenoidectomy (T&A) performed at a local general hospital due to snoring and apnea-hypopnea index (AHI) of 10–15 on multiple prior polysomnograms . Details of his anesthetic management during surgery are not available; however no immediate perioperative complications such as laryngospasm or retained pack were reported. While in recovery, he exhibited increased work of breathing, coarse breath sounds, and lethargy. He was admitted to an adult ICU and treated with IV diuretics and oxygen with continuous positive airway pressure (CPAP). He improved briefly and CPAP was stopped, but he had an episode of vomiting after administration of oral Percocet and oxygen saturation acutely dropped to the upper 60s. CPAP was restarted and saturation increased to 90%. A chest X-ray showed peribronchial and perihilar interstitial thickening and known left lateral rib deformities. Due to unstable respiratory status, he was transferred to the Pediatric ICU at the Children's Hospital of Georgia within 12 hours of surgery.2 80% to maintain sats in the 90s. Repeat chest X-rays and chest CT showed persistent, diffuse opacities. Clinical picture suggested acute respiratory distress syndrome (ARDS) and diuretic therapy was started for fluid management. Tracheal aspirate grew methicillin-susceptible staph aureus (MSSA). Direct fiberoptic bronchoscopy done on day 8 showed significant tracheomalacia and bronchomalacia. An echocardiogram on day 10 showed mildly dilated right ventricle and elevated right ventricular systolic pressure at 3/4 systemic pressure consistent with a diagnosis of pulmonary hypertension; these findings differed significantly from previous normal echocardiogram done at 14 months of age. Sildenafil was started for treatment of pulmonary hypertension and subsequent echocardiograms showed improvement in right ventricular systolic pressure. He remained intubated for ten days but eventually was extubated to noninvasive ventilatory support with BiPAP. He was weaned to room air with continued use of BiPaP at night and later discharged to a rehabilitation facility after a total inpatient stay of 30 days.On admission to our PICU he was noted to be in moderate respiratory distress with respiratory rate 56; subcostal and intercostal retractions were present. The patient's clinical picture was concerning for postobstructive pulmonary edema (POPE) although the differential diagnosis also included aspiration pneumonia. Repeat chest X-ray showed patchy infiltrates consistent with pulmonary edema. He was started on high-flow oxygen. Diuretic therapy was initiated and intravenous fluids were restricted. Pulmonary toilet was maintained with hypertonic saline and chest physiotherapy. IV dexamethasone was given to decrease airway swelling. He was noted to have poor swallowing of secretions, and a modified barium swallow done later in the course of his hospital stay confirmed dysphagia. On day 5, he developed fever and was treated empirically with ceftriaxone for pneumonia. His respiratory status continued to decline and he ultimately developed respiratory failure, requiring intubation on day 7 of hospital stay. Ventilator settings included respiratory rate 30, PEEP +9, and PC 27 with FiOWe present a case of POPE Type II after T&A in a child with Poland-Moebius syndrome. POPE (or negative pressure pulmonary edema) is a potentially fatal complication typically seen after relief of upper airway obstruction. POPE Type I develops immediately after relief of an acute airway obstruction whereas POPE Type II typically occurs after relief of chronic obstruction (as seen with obstructive sleep apnea caused by adenotonsillar hypertrophy). Patients with chronic obstruction appear to exhibit a level of autopositive end expiratory pressure (PEEP) with a concomitant increase in end expiratory lung volume. When the obstruction is relieved, lung volumes and pressures return to normal, creating a negative intrapulmonary pressure which may result in interstitial fluid transudation and pulmonary edema . POPE usIn addition to standard risk factors for post-T&A complications, including young age and AHI >5, our patient's Poland syndrome  and Moebius syndrome  undoubtedly impacted his clinical course. Poland syndrome occurs in 1 in 20,000 live births; Poland syndrome combined with Moebius syndrome has an estimated prevalence of 1 : 500,000 . DelayedThis case highlights the association between congenital upper body abnormalities with cranial nerve defects (as in Poland-Moebius syndrome) and the development of POPE with delayed resolution. This should be anticipated following surgery in any child with similar risk factors. These patients should have surgical procedures performed in a tertiary-care facility with admission to a Pediatric ICU postoperatively for optimal management of these complications.


Left ventricular rotation is an important part of myocardial mechanics during the cardiac cycle. Understanding the mechanisms of LV rotation in different cardiac diseases could play an important role for diagnosis, risk stratification and prediction of heart failure. We sought to analyze LV rotation using the feature tracking technique in patients with dilated cardiomyopathy (DCM) included in the European CMR Registry.82 Patients diagnosed with DCM and a control group consisting of 30 healthy volunteers were analyzed using dedicated feature tracking imaging software . An apical, midventricular and basal slice in short axis orientation were tracked to analyze the peak rotation of each slice. LV twist  and LV torsion (defined as the LV twist per ventricular length) were calculated.DCM patients and controls with normally directed rotation  were compared to each other table : DCM patAmongst the DCM patients an inversed rotational pattern was frequently observed Table : 57.3% oDCM is associated with an inverted direction of rotation in a significant amount of cases, predominantly affecting the LV apex. Patients with a normal direction of rotation exhibit significant lower torsion. These findings warrant further investigation including clinical follow-up data in order to analyze their impact on clinical outcome in patients with DCM.N/A.


Uganda poultry production is still faced with frequent outbreaks of Newcastle disease (ND) in the backyard free-range systems despite the accessibility of cross protective vaccines. Live bird markets and waterfowl has long been reported as a major source of disease spread as well as potential sources of avirulent strains that may mutate to virulent strains. ND-virus has been reported enzootic in Ugandan poultry but limited studies have been conducted to ascertain thermostability phenotypes of the Ugandan ND-virus strains and to understand how these relate to vaccine strains.2 and LaSota) by standard thermostability procedures and Hemagglutinin-Neuraminidase (HN) gene domains. The known pathotypes with thermostability profiles were compared at HN amino acid sequences.This study evaluated thermostability of 168 ND-virus field isolates recovered from live bird markets and waterfowls in Uganda compared to two live commercial vaccine strains (I2 heamaglutinin (HA) titers during heat treatment and the infectivity of 9.8 geometric mean of log10 EID50 % in embryonated eggs. One isolate from this study exhibited a comparable thermostability and stable infectivity titers after serial passages, to that of reference commercial vaccine was recommended for immunogenicity and protection studies.Field isolates displayed disparate heat stability and HN gene domains. Thermolabile isolates were inactivated within 15 min, while the most thermostable isolates were inactivated in 120 min. Four thermostable isolates had more than 2 logThe occurrence of ND-virus strains in waterfowl and live bird markets with disparate thermostability and varying HN gene domains indicate circulation of different thermostable and thermolabile ND-virus pathotypes in the country. Newcastle disease (ND) is a contagious poultry infection that usually invokes trade barriers and exerting great economic threats . NewcastGreat importance is attached to the thermostability of live vaccinates because of their retained potency in areas with poor transport, storage facilities, human error and power shortages. Studies in search of new thermostable isolates assess virulence of pathotypes by determining the amino acid sequences at the F protein cleavage site (FPCS), mean death time (MDT) and Intracerebral pathogenicity indices (ICPI). In areas where there is frequent use of vaccines, selective pressure leading to new strains or failed vaccination has been recorded due to the use of phylogenetically divergent vaccine strains from the circulating local ND-viruses , 28. BesHN gene is known to play crucial multifunctions in infectivity , 42. It 2 strain with well-defined genotypes. However, the recent ND-virus isolates from Ugandan live bird markets indicate a high pathogenicity and low evolution , vaccinates .