Myosin Va’s adaptor protein melanophilin enforces track selection on the microtubule and actin networks in vitro

Significance Inner organization of eukaryotic cells intimately depends on the active transport of diverse intracellular cargo on the ubiquitous actin and microtubule networks. The underlying mechanisms of such directional transport processes have been of outstanding interest. We studied a motor complex composed of Rab27a, melanophilin, and myosin Va and found, surprisingly, that the adaptor protein melanophilin toggled the binding preference toward actin or microtubules in vitro. Our results offer unexpected mechanistic insights into biasing the directionality of a moving organelle on the cytoskeleton through phospho-targeting the adaptor protein rather than its motor in vivo.</jats:p

Inhaled Formoterol-Fluticasone Single Inhaler Therapy in Asthma: Real-World Efficacy, Budget Impact, and Potential to Improve Adherence

Asthma is the commonest chronic disease affecting airways in humans and has an increasing global disease burden. Inhaled corticosteroids (ICS) are the first-line therapeutic option for asthma, and addition of a long-acting beta 2-agonist (LABA) has been shown to improve asthma control. A combination of the two agents in a single inhaler is beneficial with regard to ease of administration and patient compliance. Various ICS-LABA formulations are available across various countries in the world, one among them being formoterol-fluticasone. Both formoterol and fluticasone have pharmacologic peculiarities which places the combination in a uniquely advantageous position when it comes to asthma therapy. The present review focuses on some of the, hitherto, less explored aspects of this combination inhaler such as real-world efficacy, impact on budget allocation, results of switch-over therapy, and potential to improve adherence to asthma treatment. It also provides practical recommendations on positioning it in real-world asthma management

Efficacy of Omalizumab Therapy in an Asthmatic with Low IgE

Asthma is one of the most common respiratory diseases encountered in clinical practice. Although the vast majority of asthmatics can be adequately controlled with inhaled steroids and other preventer medications, a small proportion remain uncontrolled. Anti-IgE treatment with omalizumab has been proposed in patients as a preferred approach in step 5 asthma therapy according to GINA guidelines. Although therapy with this molecule is approved for patients with atopic asthma and pretreatment serum IgE levels of 30-1500 only, there have been a few reports of its efficacy in subjects outside this reference IgE range. We report the case of a middle-aged lady with severe corticosteroid-dependent asthma and low serum IgE levels who was successfully treated with 9 months of omalizumab therapy. She gained good asthma control and was tapered off steroid use by the fifth month of therapy with omalizumab. The case report stresses the need for further investigation into expanding the spectrum of omalizumab usage in asthma beyond the current IgE suitability range

Acute Presentation of Amiodarone Toxicity with Pleural Involvement

Amiodarone is a frequently prescribed anti-arrhythmic drug which is used to treat ventricular and supraventricular tachyarrhythmia. Although it has excellent efficacy in controlling or preventing common arrhythmias, it is potentially associated with a variety of adverse effects, the most serious of these being pulmonary toxicity. Amiodarone-associated toxicities are usually seen in solid organs like lung, spleen and thyroid due to extension of its pharmacokinetic properties. The presentation is often subacute. Acute presentation with pleural involvement is distinctly uncommon in amiodarone toxicity and can pose diagnostic challenges. Here the case presented is of a 67 year old female with multiple co-morbidities on amiodarone therapy, who presented with massive pleural effusion and respiratory failure. Typical radiological findings along with exclusion of alternate causes with appropriate tests led to a diagnosis of amiodarone toxicity involving lung parenchyma, pleura, liver and other organs. She responded to withdrawal of drug, steroid therapy and supportive care

Hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated patients with exacerbation of COPD: results from the HOPE COPD Study

Background Infectious exacerbations are crucial events that dictate the natural course of COPD patients. Pneumococcal vaccination has been shown to decrease incidence of community-acquired pneumonia in COPD patients. There is a paucity of data on outcomes of hospitalisation in pneumococcal-vaccinated COPD patients in comparison with unvaccinated subjects. The objectives of the present study were to evaluate the difference in hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated COPD subjects hospitalised with acute exacerbation. Methods This was a prospective analytical study on 120 subjects hospitalised with acute COPD exacerbation. 60 patients with prior pneumococcal vaccination and 60 unvaccinated patients were recruited. Outcomes of hospitalisation such as mortality rate, need for assisted ventilation, length of hospital stay, need for intensive care unit (ICU) care and length of ICU stay were collected and compared between two groups with appropriate statistical tools. Results 60% of unvaccinated patients (36 out of 60) required assisted ventilation, whereas only 43.3% of vaccinated subjects (26 out of 60) needed assisted ventilation (p-value of 0.04). Most of the secondary outcomes were better in the vaccinated group. The mean±SD length of ICU stay in the vaccinated group was 0.67±1.11 days compared to 1.77±1.89 days in the unvaccinated group. The mean±SD length of hospital stay was 4.50±1.64 days and 5.47±2.03 days in the vaccinated and unvaccinated group, respectively (p-value of 0.005). Conclusions COPD patients who have received prior pneumococcal vaccination have better outcomes when they are hospitalised for an acute exacerbation. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalisation with acute exacerbation

Multiple myeloma with myelomatous pleural effusion and mediastinal plasmacytoma – A rare association

Multiple myeloma, a relatively uncommon malignancy accounting for approximately 1%–2% of all cancers, is characterized by neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. While it mainly affects bone marrow, thoracic manifestations necessitating pulmonologist's attention are not infrequent. Bony involvement of the thoracic cage is the most typical thoracic manifestation of multiple myeloma, whereas less common presentations include pneumonia, pleural effusion, intraparenchymal mass lesions, lymphadenopathy of the mediastinum, reticulonodular shadows, and intrapulmonary calcifications. Myelomatous involvement of pleura with pleural effusions is very uncommon as is extramedullary plasmacytomas involving the mediastinum. We describe the case of an elderly female with multiple myeloma on chemotherapy who developed both these thoracic manifestations simultaneously. Considering her advanced age and poor performance status, family opted for the best supportive care and she succumbed to her primary disease