Johnston's organ, the Drosophila auditory organ, is anatomically very different from the mammalian organ of Corti. However, recent evidence indicates significant cellular and molecular similarities ...exist between vertebrate and invertebrate hearing, suggesting that Drosophila may be a useful platform to determine the function of the many mammalian deafness genes whose underlying biological mechanisms are poorly characterized. Our goal was a comprehensive screen of all known orthologues of mammalian deafness genes in the fruit fly to better understand conservation of hearing mechanisms between the insect and the fly and ultimately gain insight into human hereditary deafness. We used bioinformatic comparisons to screen previously reported human and mouse deafness genes and found that 156 of them have orthologues in Drosophila melanogaster. We used fluorescent imaging of T2A-GAL4 gene trap and GFP or YFP fluorescent protein trap lines for 54 of the Drosophila genes and found 38 to be expressed in different cell types in Johnston's organ. We phenotypically characterized the function of strong loss-of-function mutants in three genes expressed in Johnston's organ (Cad99C, Msp-300, and Koi) using a courtship assay and electrophysiological recordings of sound-evoked potentials. Cad99C and Koi were found to have significant courtship defects. However, when we tested these genes for electrophysiological defects in hearing response, we did not see a significant difference suggesting the courtship defects were not caused by hearing deficiencies. Furthermore, we used a UAS/RNAi approach to test the function of seven genes and found two additional genes, CG5921 and Myo10a, that gave a statistically significant delay in courtship but not in sound-evoked potentials. Our results suggest that many mammalian deafness genes have Drosophila homologues expressed in the Johnston's organ, but that their requirement for hearing may not necessarily be the same as in mammals.
Recurrent traumatic patellar tendon rupture following early repair of a primary rupture is exceedingly rare; there is little technical literature on how to manage this potentially devastating injury. ...We describe here a suture anchor–based technique for revision repair augmented with an extensor reconstruction using acellular human dermal allograft.
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Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine ...interleukin-13 (IL-13) in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM).
Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb) administered subcutaneously (s.c.). Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR) by invasive measurement of lung resistance (R(L)) and dynamic compliance (C(dyn)). Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05) the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05) the increase in baseline R(L) and the decrease in baseline C(dyn) caused by chronic exposure to inhaled HDM.
These data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.
Background. Recovery from mental illness has been described as a process involving personal growth and a search for meaning. Occupation is a primary medium for human development as well as the ...creation of life meaning, suggesting the exploration of recovery from an occupational perspective is warranted.
Purpose. To explore the experience and meaning of occupation for 13 people who self-identified as being in recovery from mental illness.
Methods. Recovery narratives were collected from participants in conversational interviews that were recorded and transcribed. The transcripts were analysed using hermeneutic phenomenology.
Findings. A range of experiences were evident in the recovery narratives, from complete disengagement to full engagement in occupations. Insights into the experience and meaning of different states of occupation were revealed.
Implications. All forms of occupational engagement, including disengagement, can be meaningful in the recovery process. Increased understanding of different modes of occupational engagement will assist therapists to support recovery more effectively.
Protein-protein interactions (PPIs) regulate assembly of macromolecular complexes, yet remain challenging to study within the native cytoplasm where they normally exert their biological effect. Here ...we miniaturize the concept of affinity pulldown, a gold-standard in vitro PPI interrogation technique, to perform nanoscale pulldowns (NanoSPDs) within living cells. NanoSPD hijacks the normal process of intracellular trafficking by myosin motors to forcibly pull fluorescently tagged protein complexes along filopodial actin filaments. Using dual-color total internal reflection fluorescence microscopy, we demonstrate complex formation by showing that bait and prey molecules are simultaneously trafficked and actively concentrated into a nanoscopic volume at the tips of filopodia. The resulting molecular traffic jams at filopodial tips amplify fluorescence intensities and allow PPIs to be interrogated using standard epifluorescence microscopy. A rigorous quantification framework and software tool are provided to statistically evaluate NanoSPD data sets. We demonstrate the capabilities of NanoSPD for a range of nuclear and cytoplasmic PPIs implicated in human deafness, in addition to dissecting these interactions using domain mapping and mutagenesis experiments. The NanoSPD methodology is extensible for use with other fluorescent molecules, in addition to proteins, and the platform can be easily scaled for high-throughput applications.
Exclusion and bypass for penetrating vascular injury remains the gold standard. Persistent hemorrhage via retrograde perfusion of the injured vessel by collateral vessels is rare and may, therefore, ...be overlooked as a cause of postoperative hemorrhage following bypass for vascular injury. We report a case of a 49-year-old male who presented to our institution 2 weeks following a bypass graft of his popliteal artery after sustaining a gunshot wound to the vessel. His ongoing complaints of pain and pressure in the popliteal fossa were found to be related to persistent collateral perfusion of the injured segment of his proximal popliteal artery. His symptoms resolved completely following coil embolization of the injured native artery. While quite rare in clinical practice, the pathophysiology of this case is analogous to persistent perfusion of the aneurysm sac following open abdominal aortic aneurysm repair or bypass and exclusion of a popliteal artery. In the setting of bypass grafting for vascular trauma, postoperative hemorrhage or compressive symptoms should prompt a complete evaluation for a potentially missed patent collateral vessel.
Background:
Patellar tendon ruptures are the third-most common injury involving the knee extensor mechanism. They typically occur in men under 40 years old as a result of eccentric quadriceps ...contraction while the knee is flexed and the foot is planted.1 The optimal treatment is surgical repair within 2 weeks of injury to prevent scar formation, degeneration, and loss of tendon excursion.
Indications:
Operative management is generally indicated for patellar tendon ruptures. In this case, a physically active, healthy 24-year-old man presented with acute pain, extensor lag, and patella alta related to a basketball injury. He was diagnosed with acute patellar tendon rupture/extensor mechanism disruption and indicated for surgery.
Technique description:
We describe a technique for primary patellar tendon repair which uses both knot-based and knotless suture anchor fixation. Using a pulley effect, sutures in the inferior patellar anchors are used to reduce and repair the patellar tendon back to its bony origin. Patellar anchor-based tapes and a suprapatellar traction suture are affixed with knotless anchors to the proximal tibia to reinforce the repair. Anchor-based suture limbs are used to repair the medial and lateral retinacula.
Results:
The senior authors’ experience with this technique has been excellent restoration of extensor mechanism function, with rehabilitation permitting early range of motion and no major complications or failures. This patient returned to unassisted activities of daily living between 8 and 12 weeks and had returned to gym workouts and recreational sports at 12 months.
Discussion/conclusion:
Biomechanical studies have demonstrated that compared with transosseous repair, suture anchor repair decreases gap formation and improves ultimate load to failure. Advantages of suture anchor repair include smaller incision, less tissue dissection, shorter operative time, and improved repair biomechanics. Our technique follows a principle of tendon repair using a high number of suture and tape limbs to span the repair. In addition, this technique incorporates a “double row” of suture anchors and spans the primary repair with a suture and tape “internal brace.”
The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Graphical Abstract
This is a visual representation of the abstract.
Arteriovenous malformations (AVMs) are a high-flow form of a vascular malformation, which can be found anywhere in the body. While historically treated surgically, a multidisciplinary approach ...utilizing multiple specialties and treatment modalities is now commonly employed. In order to effectively treat an AVM, the nidus must be targeted and eradicated, which can be done via multiple approaches. We present the case of a 43-year-old male with a gastric wall AVM, which was initially incompletely treated using a percutaneous transarterial approach. The gastric AVM was noted to have dominant drainage through a gastrorenal shunt; therefore, Balloon-occluded Retrograde Transvenous Obliteration (BRTO) was utilized to eradicate the AVM nidus. This case illustrates the utility of Interventional Radiology, specifically BRTO, as another treatment option for challenging AVMs.
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