An 80-year-old female presented with progressive breathlessness, worse on sitting or standing and relieved by lying flat. Subsequent investigations identified a patent foramen ovale (PFO) with right-to-left flow across the interatrial septum (IAS). A diagnosis of platypnoea orthodeoxia syndrome secondary to inter-atrial shunting was made. Technical features precluded a percutaneous PFO closure so an open surgical repair was performed with complete resolution of symptoms. We discuss the pathophysiology and management of platypnoea orthodeoxia syndrome.
Despite publishing surgical outcomes being a positive step forwards in the progression of England’s healthcare system, it has no doubt been faced with criticism and reservations. This review article aims to discuss the pros and cons of publishing individual surgical outcomes, as well as the challenges faced. Publishing outcomes requires data from a number of sources such as national clinical audits, hospital episode statistics, patient-reported outcomes, registers and information from revalidation. As yet, eight surgical specialties have begun publishing their data, including cardiac (coronary artery bypass graft, valve and aortic surgery), endocrine (thyroidectomy, lobectomy, isthmusectomy), orthopaedic (hip and knee replacement), urological (full and partial nephrectomies, nephroureterectomy), colorectal (bowel tumour removal), upper gastrointestinal (stomach cancer and oesophageal cancer removal, bariatric surgery), ear, nose and throat surgery (larynx, oral cavity, oropharynx, hypopharynx and salivary gland cancer removal), as well as vascular surgery (abdominal aortic aneurysm, carotid endarterectomy). However, not all procedures have been addressed. Despite the controversy surrounding the topic of publishing surgical outcomes, the advantages of reporting outcomes outweigh the disadvantages, and these challenges can be overcome, to create a more reliable, trustworthy and transparent NHS. Perhaps one of the main challenges has been the difficulty in collecting large amounts of clinically significant data able to quantify the performance of surgeons.
Alzheimer’s disease (AD) is a currently incurable neurodegenerative disorder whose treatment poses a big challenge. Proposed causes of AD include the cholinergic, amyloid and tau hypotheses. Current therapeutic treatments have been aimed at dealing with the neurotransmitter imbalance. These include cholinesterase inhibitors and N-Methyl-D-aspartate (NMDA) antagonists. However, current therapeutics have been unable to halt AD progression. Much research has gone into the development of disease-modifying drugs to interfere with the course of the disease. Approaches include secretase inhibition and immunotherapy aimed at reducing plaque deposition. However, these have not been successful in curing AD as yet. It is believed that the main reason why therapeutics have failed to work is that treatment begins too late in the course of the disease. The future of AD treatment thus appears to lie with prevention rather than cure. In this article, current therapeutics and, from there, the future of AD treatment are discussed.
University of Texas Health Science Center at Tyler – Family Medicine Residency Program, Tyler, TX The corresponding author is My-Huyen Tran, MD; [email protected]. The authors declare no conflicts of interest.
Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defects in the formation and function of lysosome-related organelles such as melanosomes. HPS in humans or mice is caused by mutations in any of 15 genes, five of which encode subunits of biogenesis of lysosome-related organelles complex (BLOC)-1, a protein complex with no known function. Here, we show that BLOC-1 functions in selective cargo exit from early endosomes toward melanosomes. BLOC-1-deficient melanocytes accumulate the melanosomal protein tyrosinase-related protein-1 (Tyrp1), but not other melanosomal proteins, in endosomal vacuoles and the cell surface due to failed biosynthetic transit from early endosomes to melanosomes and consequent increased endocytic flux. The defects are corrected by restoration of the missing BLOC-1 subunit. Melanocytes from HPS model mice lacking a different protein complex, BLOC-2, accumulate Tyrp1 in distinct downstream endosomal intermediates, suggesting that BLOC-1 and BLOC-2 act sequentially in the same pathway. By contrast, intracellular Tyrp1 is correctly targeted to melanosomes in melanocytes lacking another HPS-associated protein complex, adaptor protein (AP)-3. The results indicate that melanosome maturation requires at least two cargo transport pathways directly from early endosomes to melanosomes, one pathway mediated by AP-3 and one pathway mediated by BLOC-1 and BLOC-2, that are deficient in several forms of HPS.
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