Kinetic Evaluation of the Hypoxia Radiotracers ­ 18 FFMISO and ­ 18 F FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging / 대한핵의학회잡지

Purpose@#We evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F] fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors. @*Methods@#Sixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F] FAZA. The maximum tumor-to-muscle ratio ­(TMR max ) > 1.4 on the last image frame was used as the standard threshold to determine tumor hypoxia. The tumor time-activity curves were analyzed using irreversible and reversible two-tissue compartment models and graphical methods. T­MR max was compared with radiotracer trapping rate (k 3 ), influx rate (K i ), and distribution volume (V T ). @*Results@#Tumor hypoxia was detected in 7/8 tumors in the [18F]FMISO group and 4/8 tumors in the [18F]FAZA group. All hypoxic tumors were detected at > 120 min with [18F]FMISO and at > 60 min with [18F]FAZA. [18F]FAZA showed better fit with the reversible model. ­TMR max was strongly correlated with the irreversible parameters (k3 and Ki ) for [18F]FMISO at > 90 min and with the reversible parameter (V T ) for [18F]FAZA at > 120 min. @*Conclusions@#Our results showed that [18F]FAZA provided a promising alternative radiotracer to [18F]FMISO with detecting the presence of tumor hypoxia at an earlier time (60 min), consistent with its favorable faster kinetics. The strong correlation betwee TMR max over the 90–150 min and 120–150 min timeframes with [18F]FMISO and [18F]FAZA, respectively, with kinetic parameters associated with tumor hypoxia for each radiotracer, suggests that a static scan measurement ( ­TMR max ) is a good alternative to quantify tumor hypoxia.

Medical residents and attending physicians’ perceptions of feedback and teaching in the United States: a qualitative study / 보건의료교육평가

Purpose@#Residents and attendings agree on the importance of feedback to resident education. However, while faculty report providing frequent feedback, residents often do not perceive receiving it, particularly in the context of teaching. Given the nuanced differences between feedback and teaching, we aimed to explore resident and attending perceptions of feedback and teaching in the clinical setting. @*Methods@#We conducted a qualitative study of internal medicine residents and attendings from December 2018 through March 2019 at the Massachusetts General Hospital to investigate perceptions of feedback in the inpatient clinical setting. Residents and faculty were recruited to participate in focus groups. Data were analyzed using thematic analysis to explore perspectives and barriers to feedback provision and identification. @*Results@#Five focus groups included 33 total participants in 3 attending (n=20) and 2 resident (n=13) groups. Thematic analysis of focus group transcripts identified 7 themes which organized into 3 thematic categories: (1) disentangling feedback and teaching, (2) delivering high-quality feedback, and (3) experiencing feedback in the group setting. Residents and attendings highlighted important themes in discriminating feedback from teaching. They indicated that while feedback is reactive in response to an action or behavior, teaching is proactive and oriented toward future endeavors. @*Conclusion@#Confusion between the critical concepts of teaching and feedback may be minimized by allowing them to each have their intended impact, either in response to prior events or aimed toward those yet to take place.

A mixed-methods evaluation of the impact of a pharmacist-led feedback pilot intervention on insulin prescribing in a hospital setting.

AIMS: To explore the impact of a prescribing feedback intervention on insulin prescribing. METHODS: This was a mixed-methods study in a hospital setting. An insulin prescribing feedback intervention was delivered verbally and in writing to twelve doctors. Insulin prescribing error frequency was compared to ten doctors who had not received the feedback intervention. Insulin prescribing was audited over four weeks at the start and end of the intervention period. Semi-structured interviews were conducted with participating doctors who had received feedback, and qualitative data analysed thematically to explore the impact of the intervention on their prescribing practice. RESULTS: Prescribing data were collected on 370 insulin prescriptions with 241 errors identified. A significant reduction (χ2 = 22.6, p=<0.05) in insulin prescribing error frequency was observed in the intervention group, with a non-significant increase reported in the control group. Feedback was received positively and considered valuable by doctors, supporting development of their knowledge and skills and encouraging reflection on their prescribing performance. Doctors described enhanced confidence in insulin prescribing and a desire to improve as a prescriber and avoid harm, with feedback raising awareness of their development needs. Prescribers also described enhanced team work, with greater information and feedback seeking behavior to inform future prescribing decisions. CONCLUSIONS: Feedback has potential to improve insulin prescribing and is a valued and acceptable process intervention for doctors. The impact on insulin prescribing practice is varied and complex influencing the capability, opportunity and motivation of prescribers to adapt and evolve their behavior in response to ongoing feedback.

When physical activity meets the physical environment: precision health insights from the intersection

BACKGROUND@#The physical environment can facilitate or hinder physical activity. A challenge in promoting physical activity is ensuring that the physical environment is supportive and that these supports are appropriately tailored to the individual or group in question. Ideally, aspects of the environment that impact physical activity would be enhanced, but environmental changes take time, and identifying ways to provide more precision to physical activity recommendations might be helpful for specific individuals or groups. Therefore, moving beyond a "one size fits all" to a precision-based approach is critical.@*MAIN BODY@#To this end, we considered 4 critical aspects of the physical environment that influence physical activity (walkability, green space, traffic-related air pollution, and heat) and how these aspects could enhance our ability to precisely guide physical activity. Strategies to increase physical activity could include optimizing design of the built environment or mitigating of some of the environmental impediments to activity through personalized or population-wide interventions.@*CONCLUSIONS@#Although at present non-personalized approaches may be more widespread than those tailored to one person's physical environment, targeting intrinsic personal elements (e.g., medical conditions, sex, age, socioeconomic status) has interesting potential to enhance the likelihood and ability of individuals to participate in physical activity.

Distal Esophageal Impedance Measured by High-resolution Esophageal Manometry With Impedance Suggests the Presence of Barrett’s Esophagus

Background/Aims@#Barrett’s esophagus (BE) is characterized by intestinal metaplasia in the distal esophagus. The aims of this study are to: (1) Compare baseline distal esophageal impedance (DEI) using high-resolution esophageal manometry with impedance (HREMI) in patients with BE, esophagitis, and healthy volunteers and (2) Correlate length of low impedance on HREMI in patients with BE to the length of endoscopic BE. @*Methods@#Patients with BE or esophagitis who underwent HREMI were included. Ten volunteers had HREMI. Baseline DEI was calculated from HREMI using the landmark segment. In patients with BE, the impedance was plotted to measure the extent of plotted low impedance (PLI) and visual low impedance (VLI). Lengths of VLI and PLI were correlated to endoscopic length of BE by Prague score. @*Results@#Forty-five patients were included (16 BE; 19 esophagitis; 10 volunteers). BE patients had lower baseline DEI at the first, second, and third sensors above the lower esophageal sphincter (mean ± SEM: 1.37 ± 0.45, 0.97 ± 0.27, and 0.81 ± 0.20) compared to volunteers (8.73 ± 0.60, 8.20 ± 0.73, and 6.94 ± 0.99; P < 0.001). Baseline DEI was lower in BE than esophagitis patients (2.98 ± 0.65, 2.49 ± 0.56, and 2.01 ± 0.51) at the first, second, and third sensors (P < 0.052 for second and third sensors); ie, BE < esophagitis < controls. PLI and VLI had a stronger correlation to circumferential score (r2 = 0.84 and 0.83) than maximal score (r2 = 0.76 and 0.68). @*Conclusions@#Baseline DEI is lower in BE compared with esophagitis and healthy volunteers. The length of low impedance correlates to the endoscopic extent of BE. Thus, impedance values during HREMI may help suggest the presence and extent of BE or esophagitis.

Implications of abnormal abdominal wall computed tomographic angiography findings on postmastectomy free flap breast reconstruction

Background@#Preoperative computed tomography angiography (CTA) of the abdominal wall vessels is used when planning free flap breast reconstruction (FFBR) because it provides a surgical road map which facilitates flap harvest. However, there are few reports on the effect of abnormal findings on the operative plan. @*Methods@#We conducted a retrospective study of all FFBRs performed at a tertiary referral center over a 6-year period (November 2011 to June 2017). One consultant radiologist reported on the findings. Details on patient demographics, CTA reports, and intraoperative details were collected. @*Results@#Two hundred patients received preoperative CTAs. Fourteen percent of patients (n=28) had abnormal findings. Of these findings, 18% were vascular anomalies; 36% tumorrelated and 46% were “miscellaneous.” In four patients, findings subsequently prevented surgery; they comprised a mesenteric artery aneurysm, absent deep inferior epigastric (DIE) vessels, bilateral occluded DIE arteries, and significant bone metastases. Another patient had no suitable vessels for a free flap and the surgical plan converted to a pedicled transverse rectus abdominis musculocutaneous flap. The remaining incidental findings had no impact on the surgical plan or appropriateness of FFBR. More than one in 10 of those with abnormal findings went on to have further imaging before their operation. @*Conclusions@#CTA in FFBR can have a wider impact than facilitating surgical planning and reducing operative times. Incidental findings can influence the surgical plan, and in some instances, avoid doomed-to-fail and unsafe surgery. It is therefore important that these scans are reported by an experienced radiologist.

The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis.

Mitochondrial topoisomerase IB (TOP1MT) is a nuclear-encoded topoisomerase, exclusively localized to mitochondria, which resolves topological stress generated during mtDNA replication and transcription. Here, we report that TOP1MT is overexpressed in cancer tissues and demonstrate that TOP1MT deficiency attenuates tumor growth in human and mouse models of colon and liver cancer. Due to their mitochondrial dysfunction, TOP1MT-KO cells become addicted to glycolysis, which limits synthetic building blocks and energy supply required for the proliferation of cancer cells in a nutrient-deprived tumor microenvironment. Mechanistically, we show that TOP1MT associates with mitoribosomal subunits, ensuring optimal mitochondrial translation and assembly of oxidative phosphorylation complexes that are critical for sustaining tumor growth. The TOP1MT genomic signature profile, based on Top1mt-KO liver cancers, is correlated with enhanced survival of hepatocellular carcinoma patients. Our results highlight the importance of TOP1MT for tumor development, providing a potential rationale to develop TOP1MT-targeted drugs as anticancer therapies.

The Role of Novel Oral Anticoagulants and Antiplatelet Therapy after Percutaneous Coronary Intervention: Individualizing Therapy to Optimize Outcomes

The number of patients undergoing percutaneous coronary intervention (PCI) who mandate additional oral anticoagulant therapy has been increasing. Dual antiplatelet therapy (DAPT) is associated with reduced ischemic events including stent thrombosis, myocardial infarction and stroke following PCI. However, the tradeoff is an increased risk for bleeding while on DAPT. The addition of a novel oral anticoagulant (NOAC) further increases the likelihood of bleeding while on antiplatelet therapy. Thus, the overall risks and benefits for each patient undergoing PCI on NOAC must be assessed and therapy individualized to ensure optimal therapy for each unique situation. Patients on NOAC undergoing PCI should undergo routine assessment with intravascular imaging as the role of high-risk lesion-related features have increased importance prior to determining optimal duration of treatment with DAPT. We review the best practices for the pharmacologic management of patients requiring anticoagulation with NOAC who are treated with PCI and require antiplatelet therapy.

The Role of Novel Oral Anticoagulants and Antiplatelet Therapy after Percutaneous Coronary Intervention: Individualizing Therapy to Optimize Outcomes

The number of patients undergoing percutaneous coronary intervention (PCI) who mandate additional oral anticoagulant therapy has been increasing. Dual antiplatelet therapy (DAPT) is associated with reduced ischemic events including stent thrombosis, myocardial infarction and stroke following PCI. However, the tradeoff is an increased risk for bleeding while on DAPT. The addition of a novel oral anticoagulant (NOAC) further increases the likelihood of bleeding while on antiplatelet therapy. Thus, the overall risks and benefits for each patient undergoing PCI on NOAC must be assessed and therapy individualized to ensure optimal therapy for each unique situation. Patients on NOAC undergoing PCI should undergo routine assessment with intravascular imaging as the role of high-risk lesion-related features have increased importance prior to determining optimal duration of treatment with DAPT. We review the best practices for the pharmacologic management of patients requiring anticoagulation with NOAC who are treated with PCI and require antiplatelet therapy.

Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET)

The sigma-1 receptor (R) is a unique intracellular protein. R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of R in the brain using positron emission tomography (PET) could serve as a noninvasively tool for enhancing the understanding of the disease's pathophysiology. Moreover, R PET tracers can be used for target validation and quantification in diagnosis. Herein, we describe the radiosynthesis, PET/CT imaging of novel R C-labeled radioligands based on 6-hydroxypyridazinone, [C]HCC0923 and [C]HCC0929. Two radioligands have high affinities to R, with good selectivity. In mice PET/CT imaging, both radioligands showed appropriate kinetics and distributions. Additionally, the specific interactions of two radioligands were reduced by compounds and (self-blocking). Of the two, [C]HCC0929 was further investigated in positive ligands blocking studies, using classic R agonist SA 4503 and R antagonist PD 144418. Both R ligands could extensively decreased the uptake of [C]HCC0929 in mice brain. Besides, the biodistribution of major brain regions and organs of mice were determined . These studies demonstrated that two radioligands, especially [C]HCC0929, possessed ideal imaging properties and might be valuable tools for non-invasive quantification of R in brain.

Evaluation of the leprosy control programme surveillance system in Kwara State, Nigeria, 2010 - 2014

Objective:Leprosy is a chronic, infectious disease complicated with blindness and loss of fingers/toes in some cases. Though the disease is targeted for eradication in Nigeria, the country had the 6th highest prevalence globally in 2013. This study was conducted to evaluate the leprosy surveillance system in Kwara State, assessing its operations, attributes and determining its usefulness.Method:The 2001 updated guidelines for evaluating public health systems of Centers for Disease Control and Prevention was used. Key informant interviews were done with the State Tuberculosis and Leprosy (TBL) Control Officer, and the State Epidemiologists to assess the importance of the public health, purpose and operation of the surveillance system, resources used to operate it as well as the attributes of the system. Questionnaires were administered to Local Government Area TBL supervisors to assess the attributes of the surveillance system. Surveillance data from 2010 to 2014 was analyzed and data quality determined.Results:Incidence of leprosy over the five year period 2010 – 2014 was 62.0%, 59.0%, 54.0%, 67.0%, and 42.0% respectively, with occurrence of the multi-bacillary type in 83.1% to 90.7% newly detected cases. The system was found to be 51.0% sensitive(most hospitals do not have treatment forms for health workers use, community awareness programmes was done in 53.0% of local government areas in last 3 months, contact tracing was however always done), 90.0% simple, 93.0% acceptable and 95.0% timely. Data system was both paper and electronics, based on collection, collation, analysis and reporting done quarterly in a year. The surveillance system is donor-driven and fully integrated with that of tuberculosis and buruli ulcer. Annual surveillance expenditure was about $2 500.Conclusion:Kwara State Leprosy Surveillance System has a low sensitivity with delayed case detection. Training of health workers on early case detection, provision of treatment forms and more community awareness will improve the surveillance system’s sensitivity.

Perioperative implication of the endothelial glycocalyx / 대한마취과학회지

The endothelial glycocalyx (EG) is a gel-like layer lining the luminal surface of healthy vascular endothelium. Recently, the EG has gained extensive interest as a crucial regulator of endothelial funtction, including vascular permeability, mechanotransduction, and the interaction between endothelial and circulating blood cells. The EG is degraded by various enzymes and reactive oxygen species upon pro-inflammatory stimulus. Ischemia-reperfusion injury, oxidative stress, hypervolemia, and systemic inflammatory response are responsible for perioperative EG degradation. Perioperative damage of the EG has also been demonstrated, especially in cardiac surgery. However, the protection of the EG and its association with perioperative morbidity needs to be elucidated in future studies. In this review, the present knowledge about EG and its perioperative implication is discussed from an anesthesiologist's perspective.

Giant extraskeletal chondroma of the hand: A rare case

No abstract available.

Artificial Manduca sexta forewings for flapping-wing micro aerial vehicles: how wing structure affects performance.

A novel approach to fabricating and testing artificial insect wings has been developed. Utilizing these new techniques, locally harvested hawk moth (Manduca sexta) forewings are compared to engineered forewings with varying wing structures. A number of small, flexible engineered forewings were fabricated with identical planform size and shape but with variations in camber, ribbing, thickness and composition. A series of static and dynamic assessments compares the forewings in terms of structure and performance. Data from these experiments show that the fabrication method can produce artificial forewings with similar properties to that of M. sexta. Flexural stiffness (EI) data shows a maximum percent difference of 41% between the left and right natural M. sexta forewings, whereas engineered forewings have a maximum percent difference of 18%. When deflection is induced from the ventral side of the forewing, EI values are at least 9.1% higher than when it is induced from the dorsal side. According to simulations, approximately 57% of this difference can be attributed to the camber of the forewings. Fabricated forewings produced comparable amounts of lift to natural M. sexta forewings (1.00 gF and 0.96 gF at 25 Hz flapping frequency respectively).

Re: Neuromuscular Ultrasonography of Cranial Nerves: The Authors Respond

No abstract available.

Policy Transfer Among Regional-Level Organizations: Insights from Source Water Protection in Ontario.

Organizations at the local and regional scales often face the challenge of developing policy mechanisms rapidly and concurrently, whether in response to expanding mandates, newly identified threats, or changes in the political environment. In the Canadian Province of Ontario, rapid, concurrent policy development was considered desirable by 19 regional organizations tasked with developing policies for protection of drinking water sources under very tight and highly prescribed mandates. An explicit policy transfer approach was used by these organizations. Policy transfer refers to using knowledge of policies, programs, and institutions in one context in the development of policies, programs, and institutions in another. This paper assesses three online mechanisms developed to facilitate policy transfer for source water protection in Ontario. Insights are based on a survey of policy planners from the 19 regional organizations who used the three policy transfer tools, supplemented by an analysis of three policies created and transferred among the 19 regional source water protection organizations. Policy planners in the study indicated they had used policy transfer to develop source protection policies for their regions-a finding confirmed by analysis of the text of policies. While the online policy transfer tools clearly facilitated systematic policy transfer, participants still preferred informal, direct exchanges with their peers in other regions over the use of the internet-based policy transfer mechanisms created on their behalf.

Neuromuscular Ultrasound of Cranial Nerves

Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

Chasing Tics in the Human Brain: Development of Open, Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.

Pathogenesis of endothelial cell dysfunction in chronic kidney disease: a retrospective and what the future may hold

Cardiovascular complications dominate the landscape of chronic kidney diseases (CKD). Endothelial cell dysfunction (ECD) is a well-known culprit of cardiovascular morbidity and it develops in CKD with remarkable frequency. This brief overview of ECD in CKD scans two decades of studies performed in my laboratory, from genetic analyses to proteomic and metabolomics screens. I provide a detailed description of findings related to the premature senescence of endothelial cells, cell transition from the endothelial to mesenchymal phenotype, and stages of development of ECD. Clinical utility of some of these findings is illustrated with data on laser-Doppler flowmetry and imaging in patients with CKD. Some currently available and emerging therapeutic options for the management of ECD are briefly presented.

Double Chambered Right Ventricle with Ventricular Septal Defect in Adults: Case Series and Review of the Literature

Double-chambered right ventricle (DCRV) is an uncommon congenital anomaly in which anomalous muscle bands divide the right ventricle into two chambers; a proximal high-pressure and distal low-pressure chamber. It may be associated with mid right ventricular obstruction. It is commonly associated with other congenital anomalies, most frequently perimembranous ventricular septal defect (PM-VSD). We herein present 5 adult patients with concomitant DCRV and PM-VSD who varied in their symptomatic presentations and the ways of management.