Revisiting the original Akin technique: A comparative analysis of radiographic outcome.

BACKGROUND: The Akin osteotomy is widely used to correct the hallux valgus and different fixation techniques have been proposed. Currently most of these procedures coexist, with disagreement on which offers the best results. The aim of this study is to compare the radiological outcome of the original Akin's technique with one in which a staple was used to stabilize the osteotomy. We also assessed whether other factors unrelated to the osteosynthesis could influence the radiological outcome. METHODS: We retrospectively reviewed data from 118 patients who underwent a scarf and Akin osteotomy. In 60 patients the Akin osteotomy was fixed with a staple and in 58 cases no staple was used. Hallux valgus angle (HVA), distal articular set angle (DASA), interphalangeal angle (IPA) and tibial sesamoid position were measured. The presence of lateral cortex disruption of the phalanx was also included in the analysis. RESULTS: Six variables significantly influenced the radiological results of the Akin osteotomy: preoperative HVA, IPA and tibial sesamoid position, laterality, postoperative cortical disruption and use of a staple. CONCLUSION: Ours results suggest that the original Akin's technique seems to offer equal or better results than a variation in which a staple is added to stabilize the osteotomy. LEVEL OF EVIDENCE: This is a level III retrospective case-control study.

Proteomic profiling of the oncogenic septin 9 reveals isoform-specific interactions in breast cancer cells.

Septins are a family of multimeric GTP-binding proteins, which are abnormally expressed in cancer. Septin 9 (SEPT9) is an essential and ubiquitously expressed septin with multiple isoforms, which have differential expression patterns and effects in breast cancer cells. It is unknown, however, if SEPT9 isoforms associate with different molecular networks and functions. Here, we performed a proteomic screen in MCF-7 breast cancer cells to identify the interactome of GFP-SEPT9 isoforms 1, 4 and 5, which vary significantly in their N-terminal extensions. While all three isoforms associated with SEPT2 and SEPT7, the truncated SEPT9_i4 and SEPT9_i5 interacted with septins of the SEPT6 group more promiscuously than SEPT9_i1, which bound predominately SEPT8. Spatial mapping and functional clustering of non-septin partners showed isoform-specific differences in interactions with proteins of distinct subcellular organelles (e.g., nuclei, centrosomes, cilia) and functions such as cell signalling and ubiquitination. The interactome of the full length SEPT9_i1 was more enriched in cytoskeletal regulators, while the truncated SEPT9_i4 and SEPT9_i5 exhibited preferential and isoform-specific interactions with nuclear, signalling, and ubiquitinating proteins. These data provide evidence for isoform-specific interactions, which arise from truncations in the N-terminal extensions of SEPT9, and point to novel roles in the pathogenesis of breast cancer.

Acute Myelogenous Leukemia With Trisomy 8 and Concomitant Acquired Factor VII Deficiency.

Acquired isolated factor VII deficiency is a rare bleeding disorder and has been reported in 31 cases. This is in contrast to congenital factor VII deficiency, which while also infrequent is the most common rare congenital bleeding disorder. Acquired isolated factor VII deficiency has been described primarily in patients with solid malignancies, sepsis, and in the presence of anti-factor VII autoantibodies. We report a case of acute myelogenous leukemia with an associated trisomy 8 cytogenetic abnormality presenting with factor VII deficiency. The factor VII deficiency cleared after induction chemotherapy and with the disappearance of the cytogenetic and molecular abnormalities. We discuss a possible link between trisomy 8 and vitamin K metabolism, which might result in acquired factor VII deficiency in acute myelogenous leukemia.

Leptomeningeal Carcinomatosis From Carcinoma of Unknown Primary in a Young Patient: A Case Report and a Literature Review.

Leptomeningeal carcinomatosis, leptomeningeal meningitis, or, as referred here, leptomeningeal metastasis (LM), is a rare but frequently fatal complication seen in advanced stage of cancer either locally advanced or after a metastasis of a known primary cancer. We present a rare and uncommon case of leptomeningeal metastases from carcinoma of unknown primary. A 32-year-old female was diagnosed with LM; however, no known primary carcinoma was identified after 2 separate biopsies. The first biopsy of the right pre-tracheal lymph node showed poorly differentiated pan-keratin (AE1 and AE3) and placental alkaline phosphatase with the possibility of germ cell origin. Second cytology of cervical lymphadenopathy was remarkable for cytokeratin 7 and 20, placental alkaline phosphatase, and CDX2 suggestive of germ line tumor with both mucinous ovarian and gastrointestinal carcinomas. Unfortunately, the LM progressed rapidly despite multiple cycles of germ cell origin directed systemic and intrathecal chemotherapy, and the patient opted for hospice care without getting a chance to identify the primary source.

Inversion effects in the expert classification of mammograms and faces.

A hallmark of a perceptual expert is the ability to detect and categorize stimuli in their domain of expertise after brief exposure. For example, expert radiologists can differentiate between "abnormal" and "normal" mammograms after a 250 ms exposure. It has been speculated that rapid detection depends on a global analysis referred to as holistic perception. Holistic processing in radiology seems similar to holistic perception in which a stimulus like a face is perceived as an integrated whole, not in terms of its individual features. Holistic processing is typically subject to inversion effects in which the inverted image is harder to process/recognize. Is radiological perception similarly subject to inversion effects? Eleven experienced radiologists (> 5 years of radiological experience) and ten resident radiologists (< 5 years of radiological experience) judged upright and inverted bilateral mammograms as "normal" or "abnormal". For comparison, the same participants judged whether upright and inverted faces were "happy" or "neutral". We obtained the expected inversion effect for faces. Expression discrimination was superior for upright faces. For mammograms, experienced radiologists exhibited a similar inversion effect, showing higher accuracy for upright than for inverted mammograms. Less experienced radiology residents performed more poorly than experienced radiologists and demonstrated no inversion effect with mammograms. These results suggest that the ability to discriminate normal from abnormal mammograms is a form of learned, holistic processing.

Septins promote stress fiber-mediated maturation of focal adhesions and renal epithelial motility.

Organogenesis and tumor metastasis involve the transformation of epithelia to highly motile mesenchymal-like cells. Septins are filamentous G proteins, which are overexpressed in metastatic carcinomas, but their functions in epithelial motility are unknown. Here, we show that a novel network of septin filaments underlies the organization of the transverse arc and radial (dorsal) stress fibers at the leading lamella of migrating renal epithelia. Surprisingly, septin depletion resulted in smaller and more transient and peripheral focal adhesions. This phenotype was accompanied by a highly disorganized lamellar actin network and rescued by the actin bundling protein α-actinin-1. We show that preassembled actin filaments are cross-linked directly by Septin 9 (SEPT9), whose expression is increased after induction of renal epithelial motility with the hepatocyte growth factor. Significantly, SEPT9 overexpression enhanced renal cell migration in 2D and 3D matrices, whereas SEPT9 knockdown decreased migration. These results suggest that septins promote epithelial motility by reinforcing the cross-linking of lamellar stress fibers and the stability of nascent focal adhesions.

Novel septin 9 repeat motifs altered in neuralgic amyotrophy bind and bundle microtubules.

Septin 9 (SEPT9) interacts with microtubules (MTs) and is mutated in hereditary neuralgic amyotrophy (HNA), an autosomal-dominant neuropathy. The mechanism of SEPT9 interaction with MTs and the molecular basis of HNA are unknown. Here, we show that the N-terminal domain of SEPT9 contains the novel repeat motifs K/R-x-x-E/D and R/K-R-x-E, which bind and bundle MTs by interacting with the acidic C-terminal tails of ß-tubulin. Alanine scanning mutagenesis revealed that the K/R-R/x-x-E/D motifs pair electrostatically with one another and the tails of ß-tubulin, enabling septin­septin interactions that link MTs together. SEPT9 isoforms lacking repeat motifs or containing the HNA-linked mutation R88W, which maps to the R/K-R-x-E motif, diminished intracellular MT bundling and impaired asymmetric neurite growth in PC-12 cells. Thus, the SEPT9 repeat motifs bind and bundle MTs, and thereby promote asymmetric neurite growth. These results provide the first insight into the mechanism of septin interaction with MTs and the molecular and cellular basis of HNA.

Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia.

Establishment of epithelial polarity requires the reorganization of the microtubule (MT) cytoskeleton from a radial array into a network positioned along the apicobasal axis of the cell. Little is known about the mechanisms that spatially guide the remodeling of MTs during epithelial polarization. Septins are filamentous guanine triphosphatases (GTPases) that associate with MTs, but the function of septins in MT organization and dynamics is poorly understood. In this paper, we show that in polarizing epithelia, septins guide the directionality of MT plus end movement by suppressing MT catastrophe. By enabling persistent MT growth, two spatially distinct populations of septins, perinuclear and peripheral filaments, steer the growth and capture of MT plus ends. This navigation mechanism is essential for the maintenance of perinuclear MT bundles and for the orientation of peripheral MTs as well as for the apicobasal positioning of MTs. Our results suggest that septins provide the directional guidance cues necessary for polarizing the epithelial MT network.

Intra-operative, real-time, three-dimensional ultrasound assisted positioning of catheters in the microdialysis of glial tumours.

Microdialysis allows sampling of the extra cellular fluid of normal and pathological tissues. Accurate positioning of catheters in viable, representative tumour tissue is crucial for the accuracy and effectiveness of the technique. We have performed microdialysis with the aid of intra-operative three-dimensional ultrasonography (3D-US) to guide the placement of catheters in seven patients undergoing resection for supratentorial high-grade astrocytoma. The final position of the catheter tip membrane was confirmed by intra-operative ultrasound scanning. The accuracy of the spatial targeting was validated by pathological examination and the quality of the microdialysate was checked with ultra performance liquid chromatography-mass spectrometry. Our results indicate that intra-operative 3D-US can be used to correctly position catheters for microdialysis and allows adjustment to the catheters, when necessary, prior to the dialysis of viable target tumour tissue.

Temporal changes in myocardial salvage kinases during reperfusion following ischemia: studies involving the cardioprotective adipocytokine apelin.

INTRODUCTION: Activation of the Reperfusion Injury Salvage Kinase (RISK) pathway, which incorporates phosphatidylinositol-3-OH kinase (PI3K)-Akt/protein kinase B (PKB) and p44/42 mitogen-activated protein kinase (MAPK), underlies protection against ischemia-reperfusion (I/R) injury. The temporal nature of the activation of these RISK pathway components during reperfusion is, however, uncertain. We examined Akt and p44/42 phosphorylation in hearts subjected to ischemia and varying periods of reperfusion in the absence or presence of the putative cardioprotectant, apelin-13. Akt activity was also measured. MATERIALS AND METHODS: Langendorff perfused C57Bl/6J mouse hearts were subjected to 35 min global ischemia followed by 0, 2.5, 5 or 10 min reperfusion with or without 1 microM apelin-13. Basal and apelin-induced phosphorylation of Akt (at both the threonine 308 and serine 473 phosphorylation sites) and p44/42 during the reperfusion phase was determined by Western blotting and Akt activity measured using an Enzyme-Linked ImmunoSorbent Assay (ELISA). RESULTS: Basal phosphorylation of both Akt and p44/42 increased progressively with time of reperfusion. Apelin enhanced Akt and p44/42 phosphorylation at all reperfusion time points. Akt activity did not change under basal conditions but was increased by apelin at 5 min (NS) and 10 min (p<0.05) reperfusion. DISCUSSION: We conclude that under basal conditions Akt and p44/42 phosphorylation increases with time of reperfusion but that this is not accompanied by increased kinase (Akt) activity. On application of a cardioprotectant, however, kinase phosphorylation and activity are enhanced suggesting that it is the combination of these two mechanisms that may underly the tissue preserving actions of such agents.