Publications by authors named "Locke T"

Methicillin-resistant (MRSA) is a common cause of infection in both community and healthcare settings, and the household may be a central component linking these two environments. Strategies to prevent transmission and thereby reduce the risk of infection must be informed by a detailed understanding of local epidemiology. These data are typically lacking in many low- and middle-income countries.

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Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25-26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs.

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Calcium ions play important roles in nearly every biological process, yet whole-proteome analysis of calcium effectors has been hindered by a lack of high-throughput, unbiased, and quantitative methods to identify protein-calcium engagement. To address this, we adapted protein thermostability assays in budding yeast, human cells, and mouse mitochondria. Based on calcium-dependent thermostability, we identified 2,884 putative calcium-regulated proteins across human, mouse, and yeast proteomes.

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Clinical evidence generation from and for representative populations can be improved through increased research access and ease of trial participation. To improve access and participation, a modern trial infrastructure is needed that broadens research into more routine practice. This commentary highlights current barriers, areas of advancement, and actions needed to enable continued transformation toward a modern trial infrastructure for an improved evidence generation system.

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Background: Empty nose syndrome (ENS) is a poorly understood, debilitating condition affecting a minority of patients who underwent nasal airway surgery, most commonly following inferior turbinate surgery. Few publications have demonstrated middle turbinate resection (MTR) causing ENS, but MTR is still considered a potential cause of ENS. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) is validated for ENS diagnosis, with ENS6Q ≥ 11 considered highly suggestive of ENS.

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Article Synopsis
  • Metabolic adaptations are crucial for survival, with the mitochondrial calcium uniporter playing a key role in managing energy supply by regulating mitochondrial functions and calcium signaling.
  • The study investigates the effects of uniporter loss and gain on metabolic pathways, revealing that loss of function increases proteins involved in branched-chain amino acid (BCAA) catabolism, while specifically suppressing this pathway in liver cancer cells with high mitochondrial calcium levels.
  • The research also highlights the upregulation of the transcription factor KLF15 due to uniporter loss, linking it to changes in liver metabolism and potential complications like hyperammonemia in cancer patients.
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The Hallmark Channel, a highly watched cable network, is known for its consistently idealistic portrayals of romantic relationships. Despite its popularity, no research has examined whether increased viewership of Hallmark movies covaries with endorsement of relationship beliefs. According to cultivation theory, what we watch impacts our beliefs and perceptions of reality.

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The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generation that is not responsive to population health needs, yielding evidence that is not generalizable. Clinically integrated trials, which integrate clinical research into routine care, represent a potential solution to this challenge and an opportunity to support learning health systems.

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Calcium ions play important roles in nearly every biological process, yet whole-proteome analysis of calcium effectors has been hindered by lack of high-throughput, unbiased, and quantitative methods to identify proteins-calcium engagement. To address this, we adapted protein thermostability assays in the budding yeast, human cells, and mouse mitochondria. Based on calcium-dependent thermostability, we identified 2884 putative calcium-regulated proteins across human, mouse, and yeast proteomes.

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Objectives: The use of topical corticosteroids to manage postoperative sinonasal symptoms after endoscopic skull base surgery (ESBS) has not been well studied. We quantified long-term impact of postoperative steroid irrigations (SIs) on quality of life of patients after ESBS.

Methods: Retrospective review of patients at the University of Pennsylvania undergoing ESBS from 2010 to 2019.

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There is critical need for a predictive model of human cardiac physiology in drug development to assess compound effects on human tissues. two-dimensional monolayer cultures of cardiomyocytes provide biochemical and cellular readouts, and animal models provide information on systemic cardiovascular response. However, there remains a significant gap in these models due to their incomplete recapitulation of adult human cardiovascular physiology.

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While () bacteria are part of the human commensal flora, opportunistic invasion following breach of the epithelial layers can lead to a wide array of infection syndromes at both local and distant sites. Despite ubiquitous exposure from early infancy, the life-long risk of opportunistic infection is facilitated by a broad repertoire of virulence proteins. These proteins play a key role in inhibiting development of a long-term protective immune response by mechanisms ranging from dysregulation of the complement cascade to the disruption of leukocyte migration.

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The medical community has proposed several clinical recommendations to promote patient safety and health amid the opioid overdose public health crisis. For a frontline practicing physician, distilling the evidence and implementing the latest guidelines may prove challenging. This article aims to highlight pertinent updates and clinical care pearls as they relate to primary care management of chronic pain and opioid use disorder.

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Article Synopsis
  • Sinonasal neoplasms (both benign and malignant) are complex issues for clinicians, highlighting the need for collaboration to improve patient care, as presented in the International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT).
  • The ICSNT document organizes findings into four main sections: general principles, benign neoplasms, malignant neoplasms, and quality of life, covering 48 specific topics and providing evidence-based recommendations and summaries based on their rigor.
  • This comprehensive document reflects a collective effort from an international team to advance understanding and intervention methods for sinonasal neoplasms, while also identifying future research opportunities.
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Activation of myosin light chain kinase (MLCK) by calcium ions (Ca) and calmodulin (CaM) plays an important role in numerous cellular functions including vascular smooth muscle contraction and cellular motility. Despite extensive biochemical analysis, aspects of the mechanism of activation remain controversial, and competing theoretical models have been proposed for the binding of Ca and CaM to MLCK. The models are analytically solvable for an equilibrium steady state and give rise to distinct predictions that hold regardless of the numerical values assigned to parameters.

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A man in his 20s attended the emergency department with three days of fever, headache, reduced appetite and a sore throat. COVID-19 point-of-care test was negative. Blood cultures grew a gram-negative coccobacillus, Following an episode of confusion, MRI head revealed septic emboli.

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 Transnasal access to the anterior skull base provides a minimally invasive approach for sellar and parasellar masses compared with its open counterparts. The unique microbiome of the sinonasal mucosa provides distinct challenges not encountered with other cranial approaches. The use of antibiotics in these cases has not been standardized, and data remain scarce regarding infectious outcomes.

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Objectives: Rathke cleft cysts (RCCs) arise from the development of the Rathke pouch. Recurrence is common after either drainage or cyst removal. The endoscopic endonasal approach (EEA) is increasingly utilized for the management of RCC.

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The aim of this study is to highlight the potentially fatal risk of Strongyloidiasis Hyperinfection Syndrome for hospitalized immigrant patients with moderate to severe COVID-19 disease and undiagnosed Strongyloidiasis. We reviewed electronic medical records of immigrants from 2010 to 2022 and extracted the number of patients with eosinophilia, strongyloidiasis and COVID-19 infection, outpatient and hospitalized. While 885 outpatients were diagnosed with eosinophilia, only 356 (40.

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Background: Clubroot of canola (Brassica napus), caused by the soilborne pathogen Plasmodiophora brassicae, has become a serious threat to canola production in Canada. The deployment of clubroot-resistant (CR) cultivars is the most commonly used management strategy; however, the widespread cultivation of CR canola has resulted in the emergence of new pathotypes of P. brassicae capable of overcoming resistance.

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