SummaryBamA of Escherichia coli is an essential component of the hetero-oligomeric machinery that mediates b-barrel outer membrane protein (OMP) assembly. The C-and N-termini of BamA fold into trans-membrane b-barrel and five soluble POTRA domains respectively. Detailed characterization of BamA POTRA 1 missense and deletion mutants revealed two competing OMP assembly pathways, one of which is followed by the archetypal trimeric b-barrel OMPs, OmpF and LamB, and is dependent on POTRA 1. Interestingly, our data suggest that BamA also requires its POTRA 1 domain for proper assembly. The second pathway is independent of POTRA 1 and is exemplified by TolC. Sitespecific cross-linking analysis revealed that the POTRA 1 domain of BamA interacts with SurA, a periplasmic chaperone required for the assembly of OmpF and LamB, but not that of TolC and BamA. The data suggest that SurA and BamA POTRA 1 domain function in concert to assist folding and assembly of most b-barrel OMPs except for TolC, which folds into a unique soluble a-helical barrel and an OM-anchored b-barrel. The two assembly pathways finally merge at some step beyond POTRA 1 but presumably before membrane insertion, which is thought to be catalysed by the trans-membrane b-barrel domain of BamA.

Overdiagnosis occurs when a true abnormality is discovered, but detection of that abnormality does not benefit the patient. It should be distinguished from misdiagnosis, in which the diagnosis is inaccurate, and it is not synonymous with overtreatment or overuse, in which excess medication or procedures are provided to patients for both correct and incorrect diagnoses. Overdiagnosis for adult conditions has gained a great deal of recognition over the last few years, led by realizations that certain screening initiatives, such as those for breast and prostate cancer, may be harming the very people they were designed to protect. In the fall of 2014, the second international Preventing Overdiagnosis Conference will be held, and the British Medical Journal will produce an overdiagnosis-themed journal issue. However, overdiagnosis in children has been less well described. This special article seeks to raise awareness of the possibility of overdiagnosis in pediatrics, suggesting that overdiagnosis may affect commonly diagnosed conditions such as attention-deficit/hyperactivity disorder, bacteremia, food allergy, hyperbilirubinemia, obstructive sleep apnea, and urinary tract infection. Through these and other examples, we discuss why overdiagnosis occurs and how it may be harming children. Additionally, we consider research and education strategies, with the goal to better elucidate pediatric overdiagnosis and mitigate its influence.

edical overuse has gained traction in the national health care conversation. 1 In the United States, deeper understanding about the contributions of medical overuse to the opioid epidemic 2,3 has led to reduced prescribing by practitioners. The public is also learning about harms from inappropriate use of medical devices through articles that detail large investigations, 4 books, 5 and even film. 6 The burgeoning public conversation about overuse has been accompanied by continued efforts within the medical community to address it. Initiatives have included professional meetings (such as the Preventing Overdiagnosis 7 and High Value Practice Academic Alliance conferences) 8 ; quality improvement initiatives at the institutional, payer, and state levels 9,10 ; and targeted collections in medical journals, such as the Less is More series in JAMA Internal Medicine. The present series of updates in overuse in adult medicine [11][12][13][14][15] has given rise to updates in pediatric [16][17][18] and dermatology overuse (unpublished data, Arash Mostaghimi, Ashley Pournamdari, Elizabeth Tkachenko, John Barbieri, and Adewole Adamson, 2019). Additional consequences of overuse receiving attention is how overuse affects practitioners. A 2018 survey 19 of physicians, nurses, and advanced practice practitioners found that self-reported provision of inappropriate or futile care was common and associated with burnout. This finding replicated previous studies of critical care practitioners 20,21 and implies that reducing overuse could enhance practitioner wellness. 19 This article examines and describes 10 of the most important studies published in 2018 concerning medical overuse in the care of adult patients. We divided the articles into the following categories: overtesting, overdiagnosis, services to question, and methods to reduce overuse. IMPORTANCE Medical overuse is an important cause of patient harm and medical waste.OBSERVATION This structured literature review of English-language articles supplemented by examination of tables of contents of high-impact journals published in 2018 identified articles related to medical overuse. Articles were appraised for their methodologic quality, clinical relevance, and influence on patients. Of 1499 candidate articles, 839 addressed medical overuse. Of these, 117 were deemed to be most significant, with the 10 highestranking articles selected by author consensus. The most important articles on medical overuse identified issues with testing, including that procalcitonin does not affect antibiotic duration in patients with lower respiratory tract infection (4.2 vs 4.3 days); incidentalomas are present in 22% to 38% of common magnetic resonance imaging or computed tomography studies; 9% of women dying of stage IV cancer are still screened with mammography; and computed tomography lung cancer screening offers stable benefit and higher rates of harm for patients at lower risk. Articles related to overtreatment reported that urgent care clinics commonly overprescribe antibiotics (in 39% of...