Burnout in Surgical Residents of Underrepresented in Medicine Backgrounds: Key Influencing Factors and Possible Solutions.

INTRODUCTION: Alarming rates of burnout in surgical training pose a concern due to its deleterious effects on both patients and providers. Datum remains lacking on rates of burnout in surgical residents based on race and ethnicity. This study aims to document the frequency of burnout in surgical residents of racially underrepresented backgrounds and elucidate contributing factors. METHODS: A 35-question anonymized survey was distributed to general surgery residents from 23 programs between August 2018 and May 2019. This survey was designed from the validated Maslach Burnout Inventory, and included additional questions assessing participant demographics, educational, and social backgrounds. Responses were analyzed utilizing chi-square tests and Wilcoxon rank sum tests. There was also a free response portion of the survey which was evaluated using thematic analysis. RESULTS: We received 243 responses from 23 general surgery programs yielding a 9% (23/246) program response rate and 26% (243/935) response rate by surgical residents. One hundred and eighty-five participants (76%) identified as nonunderrepresented in medicine and 58 (24%) of participants identified as underrepresented in medicine. Fifty-three percent were male and 47% female. Overall, sixty-six percent of all surgical residents (n = 161) endorsed burnout with racially underrepresented residents reporting higher rates of burnout at 76% compared to 63% in their nonunderrepresented counterparts (P = 0.07). CONCLUSIONS: Although the generalizability of these results is limited, higher rates of reported burnout in racially underrepresented trainees noted in our study illuminates the need for continual dialogue on potential influencing factors and mitigation strategies.

Spatial and temporal analysis of road traffic crashes and ambulance responses in Lagos state, Nigeria.

BACKGROUND: Sub-Saharan African countries, Nigeria inclusive, are constrained by grossly limited access to quality pre-hospital trauma care services (PTCS). Findings from pragmatic approaches that explore spatial and temporal trends of past road crashes can inform novel interventions. To improve access to PTCS and reduce burden of road traffic injuries we explored geospatial trends of past emergency responses to road traffic crashes (RTCs) by Lagos State Ambulance Service (LASAMBUS), assessed efficiency of responses, and outcomes of interventions by local government areas (LGAs) of crash. METHODS: Using descriptive cross-sectional design and REDcap we explored pre-hospital care data of 1220 crash victims documented on LASAMBUS intervention forms from December 2017 to May 2018. We analyzed trends in days and times of calls, demographics of victims, locations of crashes and causes of delayed emergency responses. Assisted with STATA 16 and ArcGIS pro we conducted descriptive statistics and mapping of crash metrics including spatial and temporal relationships between times of the day, seasons of year, and crash LGA population density versus RTCs incidence. Descriptive analysis and mapping were used to assess relationships between 'Causes of Delayed response' and respective crash LGAs, and between Response Times and crash LGAs. RESULTS: Incidences of RTCs were highest across peak commuting hours (07:00-12:59 and 13:00-18:59), rainy season and harmattan (foggy) months, and densely populated LGAs. Five urban LGAs accounted for over half of RTCs distributions: Eti-Osa (14.7%), Ikeja (14.4%), Kosofe (9.9%), Ikorodu (9.7%), and Alimosho (6.6%). On intervention forms with a Cause of Delay, Traffic Congestion (60%), and Poor Description (17.8%), had associations with LGA distribution. Two densely populated urban LGAs, Agege and Apapa were significantly associated with Traffic Congestion as a Cause of Delay. LASAMBUS was able to address crash in only 502 (36.8%) of the 1220 interventions. Other notable outcomes include: No Crash (false calls) (26.6%), and Crash Already Addressed (22.17%). CONCLUSIONS: Geospatial analysis of past road crashes in Lagos state offered key insights into spatial and temporal trends of RTCs across LGAs, and identified operational constraints of state-organized PTCS and factors associated with delayed emergency responses. Findings can inform programmatic interventions to improve trauma care outcomes.

Phosphoprotein-based biomarkers as predictors for cancer therapy.

Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. nonsensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses. Here, we show that Cdk5 drives growth in subgroups of patients with multiple types of neuroendocrine neoplasms. Phosphoproteomics and high throughput screening identified phosphorylation sites downstream of Cdk5. These phosphorylation events serve as biomarkers and effectively pinpoint Cdk5-driven tumors. Toward achieving targeted therapy, we demonstrate that mouse models of neuroendocrine cancer are responsive to selective Cdk5 inhibitors and biomimetic nanoparticles are effective vehicles for enhanced tumor targeting and reduction of drug toxicity. Finally, we show that biomarkers of Cdk5-dependent tumors effectively predict response to anti-Cdk5 therapy in patient-derived xenografts. Thus, a phosphoprotein-based diagnostic assay combined with Cdk5-targeted therapy is a rational treatment approach for neuroendocrine malignancies.

The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Secondary and Tertiary Renal Hyperparathyroidism.

OBJECTIVE: To develop evidence-based recommendations for safe, effective, and appropriate treatment of secondary (SHPT) and tertiary (THPT) renal hyperparathyroidism. BACKGROUND: Hyperparathyroidism is common among patients with chronic kidney disease, end-stage kidney disease, and kidney transplant. The surgical management of SHPT and THPT is nuanced and requires a multidisciplinary approach. There are currently no clinical practice guidelines that address the surgical treatment of SHPT and THPT. METHODS: Medical literature was reviewed from January 1, 1985 to present January 1, 2021 by a panel of 10 experts in SHPT and THPT. Recommendations using the best available evidence was constructed. The American College of Physicians grading system was used to determine levels of evidence. Recommendations were discussed to consensus. The American Association of Endocrine Surgeons membership reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines present the epidemiology and pathophysiology of SHPT and THPT and provide recommendations for work-up and management of SHPT and THPT for all involved clinicians. It outlines the preoperative, intraoperative, and postoperative management of SHPT and THPT, as well as related definitions, operative techniques, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Preoperative and Perioperative Care, Surgical Planning and Parathyroidectomy, Adjuncts and Approaches, Outcomes, and Reoperation. CONCLUSIONS: Evidence-based guidelines were created to assist clinicians in the optimal management of secondary and tertiary renal hyperparathyroidism.

Complications of traditional bonesetting in contemporary fracture care in low- and middle-income countries: A systematic review.

OBJECTIVE: To provide an overview of the evidence on the prevalence and pattern of complications among patients treated by traditional bonesetting presenting for modern orthopaedic services in low- and middle-income countries (LMIC). METHODS: Systematic review following PRISMA guidelines. Articles were identified by searching PubMed, Embase, ScienceDirect, SCOPUS, and Web of Science using the keywords "fracture care", "traditional bonesetters" and "complications". Papers included for review were original articles set in an LMIC that directly reported the prevalence and pattern of musculoskeletal complications of traditional bonesetters' fracture treatment in LMIC settings. RESULTS: A total of 176 papers were screened for eligibility and 15 studies were finally included. Nine were prospective studies, six were retrospective studies. All were hospital-based, observational studies that investigated the outcomes of treatment of fractures by traditional bonesetters published between 1986 and 2018. In total, this review covers 1389 participants with 1470 complications of fracture treatment. CONCLUSION: Traditional bonesetting complications are associated with significant morbidity. However, traditional bonesetters have the potential to contribute positively to primary fracture care when they are trained.

Global community perception of 'surgical care' as a public health issue: a cross sectional survey.

BACKGROUND: In the last decade surgical care has been propelled into the public health domain with the establishment of a World Health Organisation (WHO) designated programme and key publications. The passing of the historic World Health Assembly Resolution (WHA) acknowledged surgical care as a vital component towards achieving Universal Health Coverage (UHC). We conducted the first worldwide survey to explore the perception of surgical care as a public health issue. METHOD: The anonymous, cross sectional survey targeted worldwide participants across a range of professional backgrounds, including non-medical using virtual snowball sampling method (in English) using Google Forms (Google Inc., Mountain View, CA, USA) from 20th February 2019 to 25th June 2019. The survey questions were designed to gauge awareness on Sustainable Development Goals (SDGs), UHC, WHO programmes and key publications on surgical care as well as perception of surgical care as a priority topic in public health. RESULTS: The survey was completed by 1954 respondents from 118 countries. Respondents were least aware of surgical care as a teaching topic in public health courses (27%; n = 526) and as a WHO programme (20%; n = 384). 82% of respondents were aware of UHC (n = 1599) and of this 72% (n = 1152) agreed that surgical care fits within UHC. While 77% (n = 1495) of respondents were aware of SDGs, only 19% (n = 370) agreed that surgery was a priority to meet SDGs. 48% (n = 941) rated surgical care as a cost-effective component of Primary Health Care. 88% (n = 1712) respondents had not read the WHA Resolution on 'Strengthening emergency and essential surgical care and anaesthesia as a component of UHC'. CONCLUSION: There is still a widespread gap in awareness on the importance of surgical care as a public health issue amongst our respondents. Surgical care was not seen as a priority to reach the SDGs, less visible as a WHO programme and not perceived as an important topic for public health courses.

Decreasing Trends in Road Traffic Injury Incidence and Mortality in Nigeria: A Ten-Year Analysis.

BACKGROUND: Road traffic accidents constitute a significant public health burden in Nigeria. In this study, we aim to (1) characterize the temporal burden of road traffic injury (RTI) and mortality rates in Nigeria over a decade, (2) identify regional RTI incidence, mortality trends, and high-risk regions, and (3) assess the impact of state population on injury and mortality. MATERIALS AND METHODS: We retrospectively reviewed aggregate state-level RTI incidence and mortality counts reported by the Federal Road Safety Corps from January 2001 through December 2010. We also reviewed population data from the National Population Commission. In addition to national analyses, regional analyses were performed in Nigeria's six geopolitical zones and one Federal Capital Territory (FCT). Regression analysis was also performed to determine the relationship between population and RTI incidence and mortality. RESULTS: The national median RTI incidence and mortality rates declined by 53% and 75%, respectively, between 2001 and 2010. Analysis by geopolitical zone yielded the greatest increases for both injury and mortality in the FCT and the greatest decreases for both in the South-South region. The average geopolitical zone, apart from the FCT, experienced a 24% decrease in the incidence rate and a 69% decrease in the mortality rate. An analysis of variance, run to assess potential differences in RTI incidence and mortality rates by state population, yielded significant values of P = 0.0023 for injury and P = 0.0002 for mortality. CONCLUSIONS: Acknowledging the potential for underreporting, a more holistic surveillance approach would generate more accurate data for future policy creation to improve clinical outcomes.

Rapid Relief: Thyroidectomy is a Quicker Cure than Radioactive Iodine Ablation (RAI) in Patients with Hyperthyroidism.

BACKGROUND: Time to hormonal control after definitive management of hyperthyroidism is unknown but may influence patient and physician decision making when choosing between treatment options. The hypothesis is that the euthyroid state is achieved faster after thyroidectomy than RAI ablation. METHODS: A retrospective review of all patients undergoing definitive therapy for hyperthyroidism was performed. Outcomes after thyroidectomy were compared to RAI. RESULTS: Over 3 years, 217 patients underwent definitive therapy for hyperthyroidism at a county hospital: 121 patients received RAI, and 96 patients underwent thyroidectomy. Age was equivalent (p = 0.72). More males underwent RAI (25% vs 15%, p = 0.05). Endocrinologists referred for both treatments equally (p = 0.82). Both treatments were offered after a minimum 1-year trial of medical management (p = 0.15). RAI patients mostly had Graves (93%), versus 73% of thyroidectomy patients (p < 0.001). Thyroidectomy patients more frequently had eye symptoms (35% vs 13%, p < 0.001), compressive symptoms (74% vs 15%, p < 0.001), or were pregnant/nursing (14% vs 0, p < 0.001). While the thyroidectomy patients had a documented discussion of all treatment modalities, 79% of RAI patients did not have a documented discussion regarding the option of surgical management (p < 0.001). Both treatment groups achieved an euthyroid state (71% vs 65%, p = 0.39). Thyroidectomy patients became euthyroid faster [3 months (2-7 months) versus 9 months (4-14 months); p < 0.001]. CONCLUSIONS: Thyroidectomy for hyperthyroidism renders a patient to an euthyroid state faster than RAI. This finding may be important for patients and clinicians considering definitive options for hyperthyroidism.

Contralateral adrenal abnormalities in Conn's syndrome.

BACKGROUND: During the course of evaluation for primary hyperaldosteronism, cross-sectional imaging is obtained in efforts to identify patients with an aldosterone producing adenoma (APA). A subset of these patients will have a synchronous, contralateral adrenal abnormality. Adrenal vein sampling (AVS) further guides clinical decision making by identifying unilateral (APA) versus bilateral hypersecretion. In the subset of patients with contralateral adrenal abnormalities, it is unclear how this affects the durability of an adrenalectomy for APA. This study characterizes this group of patients to assess the efficacy of surgical intervention. METHODS: A retrospective review of patients undergoing adrenalectomy for APA based on AVS at a university practice. Preoperative and postoperative patient characteristics, laboratory evaluations, imaging results, and final pathology were noted. RESULTS: From 2000 to 2011, 103 patients with APA underwent unilateral adrenalectomy. Eighteen patients (17%) had discordant results between AVS and imaging. Most of these patients were male (78%), and the mean age was 57 ± 13 y. Median duration of follow-up was 3.5 y [1 y, 6 y]. All patients with initial hypokalemia were rendered normokalemic after the operation. Four patients increased their antihypertensive regimen during the follow-up period. These patients all had nodular hyperplasia on final pathology. CONCLUSIONS: In patients with bilateral adrenal abnormalities who have undergone unilateral adrenalectomy for primary hyperaldosteronism, patients with clear APAs on final pathology appear to have durable outcomes after resection. Conversely, nodular hyperplasia on final pathology may be a risk factor for ongoing aldosterone hypersecretion. An algorithm for biochemical surveillance in this subset of patients should be considered.

Early endocrine attending surgeon presence increases operating room efficiency.

BACKGROUND: Preincision operating room (OR) preparation varies greatly. Cases requiring exacting preoperative setup may be more sensitive to inconsistent team members and trainees. Leadership and oversight by the surgeon may facilitate a timely start. The study hypothesized that early attending presence in the OR expedites surgery start time, improving efficiency, and decreasing cost. METHODS: Prospective data collection of endocrine surgery cases at an urban teaching hospital was performed. Time points recorded in minutes. Cost/min of OR time was $54. Patients classified as in the OR ≤10 min before attending arrival or >10 min before attending arrival. RESULTS: A total of 227 cases (166 thyroid, 54 parathyroid, 10 adrenal) were performed over 14 mo. Of the patients, 128 were in the OR ≤10 min before attending arrival, and 99 patients were >10 min (3 ± 3 min versus 35 ± 14 min, P < 0.01). The ≤10 min procedures started sooner after patient arrival in OR (40 ± 11 versus 63 ± 19, P < 0.01) which equated to $1202 of savings before incision. Although attending time in the OR before incision was equivalent between groups for adrenal and parathyroid, time to incision was shorter in the ≤10 min groups, saving $2416 ± 477 and $1458 ± 244, respectively (P < 0.01). Attending time in OR before thyroidectomy was 13 min longer in ≤10 min than >10 min (P < 0.01), but incisions were made 20 min sooner (P < 0.01) equating to $1076 ± 120 in savings. CONCLUSIONS: Early attending presence in the OR shortens time to incision. For parathyroid and adrenal cases, this does not require additional surgeon time. In ORs without consistent teams, early attending presence in the OR improves efficiency and yields significant cost savings.

Using parallel geocoding to analyse the spatial characteristics of road traffic injury occurrences across Lagos, Nigeria.

While efforts to understand and mitigate road traffic injury (RTI) occurrence have long been underway in high-income countries, similar projects in low/middle-income countries (LMICs) are frequently hindered by institutional and informational obstacles. Technological advances in geospatial analysis provide a pathway to overcome a subset of these barriers, and in doing so enable researchers to create actionable insights in the pursuit of mitigating RTI-associated negative health outcomes. This analysis develops a parallel geocoding workflow to improve investigation of low-fidelity datasets common in LMICs. Subsequently, this workflow is applied to and evaluated on an RTI dataset from Lagos State, Nigeria, minimising positional error in geocoding by incorporating outputs from four commercially available geocoders. The concordance between outputs from these geocoders is evaluated, and spatial visualisations are generated to provide insight into the distribution of RTI occurrence within the analysis region. This study highlights the implications of geospatial data analysis in LMICs facilitated by modern technologies on health resource allocation, and ultimately, patient outcomes.

Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model.

Using a mitochondria-targeted vitamin E (Mito-Vit-E) in a rat pneumonia-related sepsis model, we examined the role of mitochondrial reactive oxygen species in sepsis-mediated myocardial inflammation and subsequent cardiac contractile dysfunction. Sepsis was produced in adult male Sprague-Dawley rats via intratracheal injection of S. pneumonia (4 × 10(6) colony formation units per rat). A single dose of Mito-Vit-E, vitamin E, or control vehicle, at 21.5 µmol/kg, was administered 30 min postinoculation. Blood was collected, and heart tissue was harvested at various time points. Mito-Vit-E in vivo distribution was confirmed by mass spectrometry. In cardiac mitochondria, Mito-Vit-E improved total antioxidant capacity and suppressed H(2)O(2) generation, whereas vitamin E offered little effect. In cytosol, both antioxidants decreased H(2)O(2) levels, but only vitamin E strengthened antioxidant capacity. Mito-Vit-E protected mitochondrial structure and function in the heart during sepsis, demonstrated by reduction in lipid and protein oxidation, preservation of mitochondrial membrane integrity, and recovery of respiratory function. While both Mito-Vit-E and vitamin E suppressed sepsis-induced peripheral and myocardial production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6), Mito-Vit-E exhibited significantly higher efficacy (P < 0.05). Stronger anti-inflammatory action of Mito-Vit-E was further shown by its near-complete inhibition of sepsis-induced myeloperoxidase accumulation in myocardium, suggesting its effect on neutrophil infiltration. Echocardiography analysis indicated that Mito-Vit-E ameliorated cardiac contractility of sepsis animals, shown by improved fractional shortening and ejection fraction. Together, our data suggest that targeted scavenging of mitochondrial reactive oxygen species protects mitochondrial function, attenuates tissue-level inflammation, and improves whole organ activities in the heart during sepsis.

p66Shc mediates anoikis through RhoA.

Detachment of parenchymal cells from a solid matrix switches contextual cues from survival to death during anoikis. Marked shape changes accompany detachment and are thought to trigger cell death, although a working model to explain the coordination of attachment sensation, shape change, and cell fate is elusive. The constitutive form of the adapter Shc, p52Shc, confers survival properties, whereas the longer p66Shc signals death through association with cytochrome c. We find that cells that lack p66Shc display poorly formed focal adhesions and escape anoikis. However, reexpression of p66Shc restores anoikis through a mechanism requiring focal adhesion targeting and RhoA activation but not an intact cytochrome c-binding motif. This pathway stimulates the formation of focal adhesions and stress fibers in attached cells and tension-dependent cell death upon detachment. p66Shc may thus report attachment status to the cell by imposing a tension test across candidate anchorage points, with load failure indicating detachment.

Assessment of Knowledge, Skills, and Preparedness of General-Duty Police on Prehospital Care of Road Traffic Accident Victims in Abuja, Nigeria.

OBJECTIVES: Prompt prehospital care (PHC) is essential for improving outcomes of road traffic accident victims. Previous studies in Nigeria show that little or no PHC is delivered to trauma victims by first responders. This study was conducted to assess police officers' experience with FA/BLS, to identify gaps in their FA/BLS knowledge and skills, and assess police stations' FA/BLS equipment capacity for PHC of road traffic accident victims. METHODS: This cross-sectional study was conducted among 428 GD police in Abuja between November and December 2018. Respondents were selected using stratified random sampling with proportional allocation method. Data were collected using self-administered electronic semi-structured questionnaires. Data analysis was done using STATA v 14.0 (StataCorp, College Station, TX). Chi-square and multivariate logistic regression were used to assess associations. RESULTS: We analyzed data from 419 respondents. Almost all (90.2%) of the police were aware of FA/BLS. The proportion of police with poor, fair, and good knowledge and skills on FA/BLS were 15.3%, 79.0%, and 5.7%, respectively. Tertiary (OR = 3.35, 95% CI: 1.01-11.11, P = 0.048) and postgraduate (OR = 6.89, 95% CI: 1.63-29.19, P = 0.009) levels of education had statistically significant association with good knowledge and skills. CONCLUSION: This highlights the need to implement an educational intervention to increase FA/BLS competencies within the first responder population.

Regulation of VEGF-induced endothelial cell migration by mitochondrial reactive oxygen species.

Endothelial migration is a crucial aspect of a variety of physiologic and pathologic conditions including atherosclerosis and vascular repair. Reactive oxygen species (ROS) function as second messengers during endothelial migration. Multiple intracellular sources of ROS are regulated by cellular context, external stimulus, and the microenvironment. However, the predominant source of ROS during endothelial cell (EC) migration and the mechanisms by which ROS regulate cell migration are incompletely understood. In this study, we tested the hypothesis that mitochondria-derived ROS (mtROS) regulate EC migration. In cultured human umbilical vein endothelial cells, VEGF increased mitochondrial metabolism, promoted mtROS production, and induced cell migration. Either the targeted mitochondrial delivery of the antioxidant, vitamin E (Mito-Vit-E), or the depletion of mitochondrial DNA abrogated VEGF-mediated mtROS production. Overexpression of mitochondrial catalase also inhibited VEGF-induced mitochondrial metabolism, Rac activation, and cell migration. Furthermore, these interventions suppressed VEGF-stimulated EC migration and blocked Rac1 activation in endothelial cells. Constitutively active Rac1 reversed Mito-Vit-E-induced inhibition of EC migration. Mito-Vit-E also attenuated carotid artery reendothelialization in vivo. These results provide strong evidence that mtROS regulate EC migration through Rac-1.

Lagos state ambulance service: a performance evaluation.

OBJECTIVES: The mortality rate from road traffic accidents (RTAs) in Nigeria is almost double that of the USA. In Nigeria, the first emergency medical services (EMS) system was established in March 2001, The Lagos State Ambulance Service (LASAMBUS). The objectives of this study are to (1) determine the burden of RTAs in Lagos, (2) assess RTA call outcomes, and (3) analyze LASAMBUS's response time and causes for delay. METHODOLOGY: We reviewed completed LASAMBUS intervention forms spanning December 2017 to May 2018. We categorized the call outcomes into five groups: I. Addressed Crash, II. No Crash (False Call), III. Crash Already Addressed, IV. Did Not Respond, and V. Other. We further explored associations between the (1) causes for delay and outcomes and (2) response times and the outcomes. RESULTS: Overall, we analyzed 1352 intervention forms. We found that LASAMBUS did not address 53% of the RTA calls that they received. Of this, Outcome II. No Crash (False Call) accounted for 26% and Outcome III. Crash Already Addressed accounted for 22%. Self-reported causes for delay were recorded in 180 forms, representing 13.7% of the RTA burden. Traffic congestion accounted for 60% of this distribution. CONCLUSION: LASAMBUS response rates are significantly lower than response rates in high-income countries such as the USA and lead to increased RTA mortality rates. Eliminating causes for delay will improve both LASAMBUS effectiveness and RTA victims' health outcomes. Changing the public perception of LASAMBUS and standardizing LASAMBUS' contact information will aid this as well.

Burn serum causes a CD14-dependent mitochondrial damage in primary cardiomyocytes.

Studies from animal models suggest that myocardial mitochondrial damage contributes to cardiac dysfunction after burn injury. In this report, we used an ex vivo model of primary cardiomyocyte culture to investigate the mechanisms of burn-induced mitochondrial impairment. Briefly, blood serum was collected from Sprague-Dawley (SD) rats subjected to 40% total body surface area burn and added (10% vol/vol) to primary cardiomyocytes prepared from SD rats. The effect of the burn serum on mitochondrial function and membrane integrity in the myocytes was analyzed. Exposure of myocytes to burn serum doubled the mitochondrial membrane damage measured by two independent assays. This treatment also significantly elevated mitochondrial oxidative stress, indicated by a more than 30% increase in lipid oxidation. Downregulation of mitochondrial antioxidant defense was also evident since the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were reduced by about 30% and 50%, respectively. Burn serum also induced deficiency of mitochondrial metabolism, indicated by a 30% decrease in the activity of cytochrome c oxidase. These mitochondrial dysfunctions appear to be generated by oxidative stress because burn serum induced a significant increase of mitochondrial oxygen species (mtROS) in cardiomyocytes, and pretreatment of cardiomyocytes with the antioxidant N-acetyl-cysteine prevented the mitochondrial damages induced by burn serum. Remarkably, the increase in mtROS was abolished by an antibody-mediated blockade of CD14. Furthermore, burn injury-induced mitochondrial damage in cardiomyocytes was prevented in CD14 knockout mice. Taken together, these data suggested that burn injury produces CD14-dependent mitochondrial damage via oxidative stress in myocardium.

Subcellular targeting of oxidants during endothelial cell migration.

Endogenous oxidants participate in endothelial cell migration, suggesting that the enzymatic source of oxidants, like other proteins controlling cell migration, requires precise subcellular localization for spatial confinement of signaling effects. We found that the nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase adaptor p47(phox) and its binding partner TRAF4 were sequestered within nascent, focal complexlike structures in the lamellae of motile endothelial cells. TRAF4 directly associated with the focal contact scaffold Hic-5, and the knockdown of either protein, disruption of the complex, or oxidant scavenging blocked cell migration. An active mutant of TRAF4 activated the NADPH oxidase downstream of the Rho GTPases and p21-activated kinase 1 (PAK1) and oxidatively modified the focal contact phosphatase PTP-PEST. The oxidase also functioned upstream of Rac1 activation, suggesting its participation in a positive feedback loop. Active TRAF4 initiated robust membrane ruffling through Rac1, PAK1, and the oxidase, whereas the knockdown of PTP-PEST increased ruffling independent of oxidase activation. Our data suggest that TRAF4 specifies a molecular address within focal complexes that is targeted for oxidative modification during cell migration.

Rapid cortisol assays improve the success rate of adrenal vein sampling for primary aldosteronism.

OBJECTIVE: We hypothesized that an adrenal vein sampling (AVS) algorithm incorporating rapid cortisol assays, which enables resampling of the adrenal veins, would improve the success rate by a team of radiologists. SUMMARY BACKGROUND DATA: AVS is the most accurate means to localize aldosterone production in primary aldosteronism (PA). However, cannulation of the right adrenal vein (RAV) is difficult, and success is assumed from venography without the support of steroid assays. Furthermore, few institutions can assign all studies to 1 dedicated and experienced AVS interventional radiologist. METHODS: Retrospective chart review of patients with PA at our university hospitals who underwent AVS. We compared results for 30 AVS studies incorporating rapid cortisol assays with 30 conventional AVS studies. RESULTS: The success rate for the control period was 73% (22/30 studies). For the first 30 studies after incorporating rapid cortisol assay, the success rate increased to 97% (29/30 studies). Resampling the RAV was required for 2 studies, and prolonged sheath insertion did not cause any complications. CONCLUSIONS: High AVS success rates may be achieved by a team of interventional radiologists at 1 center using defined AVS protocols. Rapid cortisol assay allows for resampling of the RAV and improves AVS success rates.

When policy meets the pedal: A reduction in motorcyclist fatalities following the implementation of a road traffic law in Lagos, Nigeria.

Objective: The Lagos State Road Traffic Law of 2012 sought to curb reckless okada use and the objective of this study is to determine its impact on motorcyclist fatalities in Nigeria's most densely populated state. This is the first study to date that analyzes the potential impact of the Law on motorcyclist fatalities across Lagos State.Methods: We retrospectively reviewed monthly motorcyclist fatalities in Lagos between January 2012 and December 2015. We analyzed the data using Geographic Information Systems (GIS) software, and used Quantum GIS ver. 2.16.2 to create maps illustrating the spatial-epidemiological distribution of motorcyclist fatalities across Lagos' health facilities. The data was collated into three eight-month periods for analysis (pre-intervention, immediate post-intervention, and sustained post-intervention). Period 1 was January to August 2012, Period 2 was September 2012 to April 2013, and Period 3 was May to December 2013. The data were compared in SPSS using the Welch's ANOVA and Tanhame (post-hoc) tests with a 5% significance level.Results: Motorcyclist fatalities in Lagos fell by an average of 76% over the study period. Over 55% of the fatalities were recorded in five health facilities, located in an area of high road network density. The number of newly registered motorcycles also declined by an average of 69%. The Welch's ANOVA yielded a statistically significant difference between the Periods' means (p < 0.0001). The Tamhane post-hoc test showed significant differences in the mean decrease in fatalities between Period 1 and Period 2 (p = 0.002), and Period 1 and Period 3 (p < 0.0001).Conclusions: This study shows a significant decline in motorcyclist fatalities following the implementation of the Lagos State Road Traffic Law of 2012. A more comprehensive approach to data collection along with an updated law could contribute towards a sustainable reduction of motorcyclist mortality.