bluuebunny/crossref_metadata_2025 huggingface dataset:
Transition metal ion FRET to measure short-range distances at the intracellular surface of the plasma membrane
Authors: Gordon Sharona E. , Senning Eric N. , Aman Teresa K. , Zagotta William N.
Published: January 2016

Biological membranes are complex assemblies of lipids and proteins that serve as platforms for cell signaling. We have developed a novel method for measuring the structure and dynamics of the membrane based on fluorescence resonance energy transfer (FRET). The method marries four technologies: (1) unroofing cells to isolate and access the cytoplasmic leaflet of the plasma membrane; (2) patch-clamp fluorometry (PCF) to measure currents and fluorescence simultaneously from a membrane patch; (3) a synthetic lipid with a metal-chelating head group to decorate the membrane with metal-binding sites; and (4) transition metal ion FRET (tmFRET) to measure short distances between a fluorescent probe and a transition metal ion on the membrane. We applied this method to measure the density and affinity of native and introduced metal-binding sites in the membrane. These experiments pave the way for measuring structural rearrangements of membrane proteins relative to the membrane.
Genetic delineation of local provenance defines seed collection zones along a climate gradient
Authors: Hufford Kristina M. , Veneklaas Erik J. , Lambers Hans , Krauss Siegfried L.
Published: January 2016

Efforts to re-establish native plant species should consider intraspecific variation if we are to restore genetic diversity and evolutionary potential. Data describing spatial genetic structure and the scale of adaptive differentiation are needed for restoration seed sourcing. Genetically defined provenance zones provide species-specific guidelines for the distance within which seed transfer likely maintains levels of genetic diversity and conserves locally adapted traits. While a growing number of studies incorporate genetic marker data in delineation of local provenance, they often fail to distinguish the impacts of neutral and non-neutral variation. We analysed population genetic structure for 134 amplified fragment length polymorphism (AFLP) markers in Stylidium hispidum (Stylidiaceae) along a north–south transect of the species' range with the goal to estimate the distance at which significant genetic differences occur among source and recipient populations in restoration. In addition, we tested AFLP markers for signatures of selection, and examined the relationship of neutral and putatively selected markers with climate variables. Estimates of population genetic structure revealed significant levels of differentiation (Φ PT = 0.23) and suggested a global provenance distance of 45 km for pairwise comparisons of 16 populations. Of the 134 markers, 13 exhibited evidence of diversifying selection (Φ PT = 0.52). Using data for precipitation and thermal gradients, we compared genetic, geographic and environmental distance for subsets of neutral and selected markers. Strong isolation by distance was detected in all cases, but positive correlations with climate variables were present only for markers with signatures of selection. We address findings in light of defining local provenance in ecological restoration.
Effectiveness of Herpes Zoster Vaccine in Patients 60 Years and Older With End-stage Renal Disease
Authors: Tseng Hung Fu , Luo Yi , Shi Jiaxiao , Sy Lina S. , Tartof Sara Y. , Sim John J. , Hechter Rulin C. , Jacobsen Steven J.
Published: January 2016

Background.  Unlike in a healthy population, the protection of herpes zoster (HZ) vaccine in end-stage renal disease (ESRD) patients might be insufficient, considering data demonstrating suboptimal response to other vaccines. The study evaluates the association between HZ vaccination and the subsequent HZ risk among ESRD patients.

Methods.  This cohort study included ESRD patients age ≥60 years who were enrolled in Kaiser Permanente Southern California. The vaccinated cohort included 582 patients who received HZ vaccine during 01/01/2007 through 12/31/2013. Each vaccinated patient was matched to five unvaccinated patients on age, sex, and dialysis duration. Subjects were passively followed through their electronic health records to identify HZ incidence. Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) associated with vaccination. Kaplan–Meier estimates of the cumulative incidence were generated.

Results.  The number of HZ cases was 16 in 1373 person-years (11.7 per 1000 person-years; 95% CI, 7.1–19.0) among the vaccinated and 126 in 5644 person-years (22.3 per 1000 person-years; 95% CI, 18.7–26.6) among the unvaccinated. The 36-month cumulative risk of incident HZ was 4.1% and 6.6%, respectively. HZ vaccination was associated with a reduced risk of HZ (adjusted HR = 0.49; 95% CI, .29–.85). The reduced risk seems more prominent if the vaccine is given within two years of dialysis initiation.

Conclusions.  Among ESRD patients age ≥60 years, receipt of HZ vaccine was associated with a lower incidence of HZ. In addition, HZ vaccination soon after the initiation of dialysis may provide greater protection.
Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis
Authors: Rolfes Melissa A. , Rhein Joshua , Schutz Charlotte , Taseera Kabanda , Nabeta Henry W. , Huppler Hullsiek Kathy , Akampuira Andrew , Rajasingham Radha , Musubire Abdu , Williams Darlisha A. , Thienemann Friedrich , Bohjanen Paul R. , Muzoora Conrad , Meintjes Graeme , Meya David B. , Boulware David R.
Published: January 2016

Background.  Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%–50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort.

Methods.  Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7–1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by “enhanced consolidation” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1–2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression.

Results.  Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6–2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity.

Conclusions.  Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes.
Legionellosis Outbreak Associated With a Hotel Fountain
Authors: Smith Shamika S. , Ritger Kathy , Samala Usha , Black Stephanie R. , Okodua Margaret , Miller Loretta , Kozak-Muiznieks Natalia A. , Hicks Lauri A. , Steinheimer Craig , Ewaidah Saadeh , Presser Lance , Siston Alicia M.
Published: January 2016

Background.  In August 2012, the Chicago Department of Public Health (CDPH) was notified of acute respiratory illness, including 1 fatality, among a group of meeting attendees who stayed at a Chicago hotel during July 30–August 3, 2012. Suspecting Legionnaires' disease (LD), CDPH advised the hotel to close their swimming pool, spa, and decorative lobby fountain and began an investigation.

Methods.  Case finding included notification of individuals potentially exposed during July 16–August 15, 2012. Individuals were interviewed using a standardized questionnaire. An environmental assessment was performed.

Results.  One hundred fourteen cases were identified: 11 confirmed LD, 29 suspect LD, and 74 Pontiac fever cases. Illness onsets occurred July 21–August 22, 2012. Median age was 48 years (range, 22–82 years), 64% were male, 59% sought medical care (15 hospitalizations), and 3 died. Relative risks for hotel exposures revealed that persons who spent time near the decorative fountain or bar, both located in the lobby were respectively 2.13 (95%, 1.64–2.77) and 1.25 (95% CI, 1.09–1.44) times more likely to become ill than those who did not. Legionella pneumophila serogroup 1 was isolated from samples collected from the fountain, spa, and women's locker room fixtures. Legionella pneumophila serogroup 1 environmental isolates and a clinical isolate had matching sequence-based types. Hotel maintenance records lacked a record of regular cleaning and disinfection of the fountain.

Conclusions.  Environmental testing identified Legionella in the hotel's potable water system. Epidemiologic and laboratory data indicated the decorative fountain as the source. Poor fountain maintenance likely created favorable conditions for Legionella overgrowth.
Linezolid in the Starter Combination for Multidrug-Resistant Tuberculosis: Time to Move on to Group Four?
Authors: Grard Soazic , Catho Gaud , Valour Florent , Bouaziz Anissa , Perpoint Thomas , Braun Evelyne , Biron François , Miailhes Patrick , Ferry Tristan , Chidiac Christian , Souquet Pierre-Jean , Couraud Sébastien , Lina Gérard , Goutelle Sylvain , Veziris Nicolas , Dumitrescu Oana , Ader Florence ,   for the Lyon TB Study Group, Ader F. , Biron F. , Boibieux A. , Bouaziz A. , Bouledrak K. , Braun E. , Catho G. , Chidiac C. , Chumbi-Flores W. , Couraud S. , Devouassoux G. , Dumitrescu O. , Ferry T. , Freymond N. , Gardes S. , Gerbier-Colomban S. , Gillet Y. , Goutelle S. , Grando J. , Grima R. , Hees L. , Jubin V. , Kiakouama-Maleka L. , Lina G. , Maury J.M. , Miailhes P. , Perpoint T. , Perrot Em. , Perrot Emm , Reix P. , Renaud-Baron A.S. , Ronin V. , Senechal A. , Souquet P.J. , Thai Van H. , Tronc F. , Valour F. , Vanhems P.
Published: January 2016

Linezolid (LNZ), a group 5 antituberculous drug (unclear efficacy), was used in the starter regimens of 23 adults with multidrug-resistant tuberculosis. The LNZ-containing regimens were effective in achieving culture conversions and relapse-free outcomes. The most frequent LNZ-related side effect was neuropathy. We propose that LNZ should be reclassified among bactericidal second-line drugs.
Candida Arthritis: Analysis of 112 Pediatric and Adult Cases
Authors: Gamaletsou Maria N. , Rammaert Blandine , Bueno Marimelle A. , Sipsas Nikolaos V. , Moriyama Brad , Kontoyiannis Dimitrios P. , Roilides Emmanuel , Zeller Valerie , Taj-Aldeen Saad J. , Miller Andy O. , Petraitiene Ruta , Lortholary Olivier , Walsh Thomas J.
Published: January 2016

Background.  Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood.

Methods.  Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome.

Results.  Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1–84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (≥3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10–141) and C reactive protein 26 mg/dL (0.5–95). Synovial fluid median white blood cell count was 27 500/µL (range, 100–220 000/µL) with 90% polymorphonuclear neutrophils (range, 24–98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%.

Conclusion.  Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy.
Clinical Care Pathways for Patients With Hepatitis C: Reducing Critical Barriers to Effective Treatment
Authors: Howes Nik , Lattimore Sam , Irving William Lucien , Thomson Brian James
Published: January 2016

Background.  Engagement of individuals infected with hepatitis C virus (HCV) with care pathways remains a major barrier to realizing the benefits of new and more effective antiviral therapies. After an exploratory study, we have undertaken an evidence-based redesign of care pathways for HCV, including the following: (1) reflex testing of anti-HCV-positive samples for HCV RNA; (2) annotation of laboratory results to recommend referral of actively infected patients to specialist clinics; (3) educational programs for primary care physicians and nurses; and (4) the establishment of needs-driven community clinics in substance misuse services.

Methods.  In this study, we conducted a retrospective cohort study of progression through care pathways of individuals with a new diagnosis of HCV infection made between January 2010 and January 2012. We also analyzed patient flow through new care pathways and compared this with our baseline study of identical design.

Results.  A total of 28 980 samples were tested for anti-HCV antibody during the study period and yielded 273 unique patients with a new diagnosis of HCV infection. Of these, 38% were tested in general practice, 21% were tested in substance misuse services, 23% were tested in secondary care, and 18% were tested in local prisons. Overall, 80% of patients were referred to specialist clinics, 70% attended for assessment, and 38% commenced treatment, in comparison to 49%, 27%, and 10%, respectively, in the baseline study. Referral rates from all testing sources improved.

Conclusions.  This study provides timely evidence that progression through care pathways can be enhanced, and it demonstrates reduction of key barriers to eradication of HCV.
Is Emtricitabine-Tenofovir Disoproxil Fumarate Pre-exposure Prophylaxis for the Prevention of Human Immunodeficiency Virus Infection Safer Than Aspirin?
Authors: Kojima Noah , Klausner Jeffrey D.
Published: January 2016

Background.  The safety and effectiveness studies of emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for human immunodeficiency virus (HIV) infection pre-exposure prophylaxis (PrEP) in men and women showed that daily use reduced the risk of HIV acquisition, but there still may concerns about safety.

Methods.  A narrative review was done in September 2015 comparing the 5 major studies on PrEP for HIV infection—Preexposure Prophylaxis Initiative (N = 2499; 3324 person-years), Partners Preexposure Prophylaxis (N = 4747; 7830 person-years), TDF2 (N = 1219; 1563 person-years), Preexposure Prophylaxis Trial for HIV Prevention among African Women (N = 2056; 1407 person-years), and Vaginal and Oral Interventions to Control the Epidemic (N = 4969; 5509 person-years)—and the 2 major studies on aspirin safety—Physicians' Health Study (N = 22 071; over 110 000 person-years) and the Women's Health Study (N = 39 876; approximately 400 000 person-years). The numbers needed to harm (NNH) were calculated for FTC-TDF for HIV infection PrEP and aspirin.

Results.  The NNH for FTC-TDF in men who have sex with men and transgender women was 114 for nausea and 96 for unintentional weight loss; in heterosexual couples, the NNH was 68 for moderate decreased absolute neutrophil count. For aspirin, the NNH was 909 for major gastrointestinal bleeding, 123 for any gastrointestinal bleeding, and 15 for any bleeding problems in men. In women, the NNH for easy bruising was 10.

Conclusions.  We conclude that FTC-TDF for PrEP for HIV infection favorably compares with aspirin in terms of user safety. Although long-term studies are needed, providers should feel reassured about the safety of short- and medium-term PrEP for HIV infection with FTC-TDF.
Strigolactone-Induced Putative Secreted Protein 1 Is Required for the Establishment of Symbiosis by the Arbuscular Mycorrhizal Fungus Rhizophagus irregularis
Authors: Tsuzuki Syusaku , Handa Yoshihiro , Takeda Naoya , Kawaguchi Masayoshi
Published: January 2016

Arbuscular mycorrhizal (AM) symbiosis is the most widespread association between plants and fungi. To provide novel insights into the molecular mechanisms of AM symbiosis, we screened and investigated genes of the AM fungus Rhizophagus irregularis that contribute to the infection of host plants. R. irregularis genes involved in the infection were explored by RNA-sequencing (RNA-seq) analysis. One of the identified genes was then characterized by a reverse genetic approach using host-induced gene silencing (HIGS), which causes RNA interference in the fungus via the host plant. The RNA-seq analysis revealed that 19 genes are up-regulated by both treatment with strigolactone (SL) (a plant symbiotic signal) and symbiosis. Eleven of the 19 genes were predicted to encode secreted proteins and, of these, SL-induced putative secreted protein 1 (SIS1) showed the largest induction under both conditions. In hairy roots of Medicago truncatula, SIS1 expression is knocked down by HIGS, resulting in significant suppression of colonization and formation of stunted arbuscules. These results suggest that SIS1 is a putative secreted protein that is induced in a wide spatiotemporal range including both the presymbiotic and symbiotic stages and that SIS1 positively regulates colonization of host plants by R. irregularis.
Mild Sedation Exacerbates or Unmasks Focal Neurologic Dysfunction in Neurosurgical Patients with Supratentorial Brain Mass Lesions in a Drug-specific Manner
Authors: Lin Nan , Han Ruquan , Zhou Jianxin , Gelb Adrian W.
Published: January 2016

AbstractAbstract

Mild sedation with propofol and midazolam exacerbated neurologic deficits to a greater extent than fentanyl or dexmedetomidine; the latter had the least effect on neurologic function. The change in neurologic function in patients with preexisting brain lesions is produced in a drug-specific effect and is not due to nonspecific sedation.

Background

Sedation is commonly used in neurosurgical patients but has been reported to produce transient focal neurologic dysfunction. The authors hypothesized that in patients with frontal–parietal–temporal brain tumors, focal neurologic deficits are unmasked or exacerbated by nonspecific sedation independent of the drug used.

Methods

This was a prospective, randomized, single-blind, self-controlled design with parallel arms. With institutional approval, patients were randomly assigned to one of the four groups: “propofol,” “midazolam,” “fentanyl,” and “dexmedetomidine.” The sedatives were titrated by ladder administration to mild sedation but fully cooperative, equivalent to Observer’s Assessment of Alertness and Sedation score = 4. National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurologic function before and after sedation. The study’s primary outcome was the proportion of NIHSS-positive change in patients after sedation to Observer’s Assessment of Alertness and Sedation = 4.

Results

One hundred twenty-four patients were included. Ninety had no neurologic deficits at baseline. The proportion of NIHSS-positive change was midazolam 72%, propofol 52%, fentanyl 27%, and dexmedetomidine 23% (P less than 0.001 among groups). No statistical difference existed between propofol and midazolam groups (P = 0.108) or between fentanyl and dexmedetomidine groups (P = 0.542). Midazolam and propofol produced more sedative-induced focal neurologic deficits compared with fentanyl and dexmedetomidine. The neurologic function deficits were mainly limb motor weakness and ataxia. Patients with high-grade gliomas were more susceptible to the induced neurologic dysfunction regardless of the sedative.

Conclusions

Midazolam and propofol augmented or revealed neurologic dysfunction more frequently than fentanyl and dexmedetomidine at equivalent sedation levels. Patients with high-grade gliomas were more susceptible than those with low-grade gliomas.
Common Anesthetic-binding Site for Inhibition of Pentameric Ligand-gated Ion Channels
Authors: Kinde Monica N. , Bu Weiming , Chen Qiang , Xu Yan , Eckenhoff Roderic G. , Tang Pei
Published: January 2016

AbstractAbstract

Using ELIC, a prokaryotic pentameric ligand-gated ion channel (pLGIC) Erwinia chrysanthemi, as a model, propofol is shown to bind in a transmembrane intrasubunit pocket that overlaps anesthetic-binding sites previously identified in other pLGICs. The functional relevance of this binding site is demonstrated by analysis of chimeric receptors, which suggests that the transmembrane intrasubunit site is a common binding site for anesthetic inhibition of cationic pLGICs.

Supplemental Digital Content is available in the text.

Background

Identifying functionally relevant anesthetic-binding sites in pentameric ligand-gated ion channels (pLGICs) is an important step toward understanding the molecular mechanisms underlying anesthetic action. The anesthetic propofol is known to inhibit cation-conducting pLGICs, including a prokaryotic pLGIC from Erwinia chrysanthemi (ELIC), but the sites responsible for functional inhibition remain undetermined.

Methods

We photolabeled ELIC with a light-activated derivative of propofol (AziPm) and performed fluorine-19 nuclear magnetic resonance experiments to support propofol binding to a transmembrane domain (TMD) intrasubunit pocket. To differentiate sites responsible for propofol inhibition from those that are functionally irrelevant, we made an ELIC-γ-aminobutyric acid receptor (GABAAR) chimera that replaced the ELIC-TMD with the α1β3GABAAR-TMD and compared functional responses of ELIC-GABAAR and ELIC with propofol modulations.

Results

Photolabeling showed multiple AziPm-binding sites in the extracellular domain (ECD) but only one site in the TMD with labeled residues M265 and F308 in the resting state of ELIC. Notably, this TMD site is an intrasubunit pocket that overlaps with binding sites for anesthetics, including propofol, found previously in other pLGICs. Fluorine-19 nuclear magnetic resonance experiments supported propofol binding to this TMD intrasubunit pocket only in the absence of agonist. Functional measurements of ELIC-GABAAR showed propofol potentiation of the agonist-elicited current instead of inhibition observed on ELIC.

Conclusions

The distinctly different responses of ELIC and ELIC-GABAAR to propofol support the functional relevance of propofol binding to the TMD. Combining the newly identified TMD intrasubunit pocket in ELIC with equivalent TMD anesthetic sites found previously in other cationic pLGICs, we propose this TMD pocket as a common site for anesthetic inhibition of pLGICs.
Internet-administered Health-related Quality of Life Questionnaires Compared With Pen and Paper in an Adolescent Scoliosis Population: A Randomized Crossover Study
Authors: Nitikman Michael , Mulpuri Kishore , Reilly Christopher W.
Published: January 2016

Background:

Modern technology puts into question the effectiveness of using pen and paper as a means of collecting information from web-enabled patients. This study aimed to validate and test the reliability of using the Internet as a method of administering health-related quality of life questionnaires in a pediatric spine population.

Methods:

A prospective randomized crossover study was conducted. Patients aged 11 to 18 with idiopathic scoliosis were invited to participate, and informed consent was obtained from a scoliosis outpatient clinic setting. Participants were randomized to one of 4 groups determining the method of questionnaire administration [Scoliosis Research Society 30 (SRS-30) and Pediatric Outcomes Data Collection Instrument (PODCI)]. Both questionnaires were completed at 2 separate timepoints and 2 weeks apart to prevent recall bias. Groups included: Paper/Paper, Paper/Internet, Internet/Paper, and Internet/Internet. Paired-samples t tests were used to determine the test-retest reliability of each group. Analysis was stratified for surveys returned within or outside of the allotted 4-week timeframe following enrollment.

Results:

Of the 96 participants who completed and returned both sets of questionnaires, 26 were allocated to the Paper/Paper group (27%), 20 to the Paper/Internet group (21%), 26 to the Internet/Paper group (27%), and 24 to the Internet/Internet group (25%). The second iteration of questionnaires was returned on time by 69 of the participants (71.2%). Of the late questionnaires, 18 (67%) were paper forms. Overall, no differences were observed between Internet-administered compared with pen and paper–administered questionnaires (P=0.206). No differences were observed within any group individually for either the SRS-30 or PODCI questionnaire. In addition, no significant differences were observed within groups for surveys returned within or outside of the 4-week timeframe. Eighty-four percent of the participants who completed both paper and Internet versions of the questionnaires reported a preference of the Internet.

Conclusion:

Internet administration of both the SRS-30 and PODCI questionnaires is a valid and reliable method of acquiring health-related quality of life information in this population

Level of Evidence:

Level II—therapeutic study.
The Impact of Child Safety Restraint Status and Age in Motor Vehicle Collisions in Predicting Type and Severity of Bone Fractures and Traumatic Injuries
Authors: Loftis Christopher M. , Sawyer Jeffrey R. , Eubanks James W. , Kelly Derek M.
Published: January 2016

Background:

Although morbidity and mortality in children increases in motor vehicle collisions (MVC) if child restraints are not used, no data exist correlating specific injuries with proper or improper use of safety restraints or age. The purpose of this study was to evaluate correlations between childhood MVC injuries, age, and restraint status.

Methods:

A medical record search for pediatric patients involved in a MVC was conducted at a pediatric hospital (level 1 trauma). Charts were reviewed for demographics and injury-specific information. Patients were grouped by age, restraint use, and injuries.

Results:

Nine hundred sixty-seven patients ≤12 years (average age 6.39 y) were identified. Being properly restrained was most common in all age groups except the 4- to 8-year age group in which being improperly restrained was most common. Unrestrained patients were most commonly found in the 9- to 12-year age group. A statistically significant difference was not observed for orthopaedic injuries among the restraint groups, but internal thoracic injuries, open head wound, and open upper extremity wounds were significantly more common in improperly or unrestrained patients. Improperly restrained infants had a significantly higher rate of intracranial bleeds and abrasions than those properly restrained. Unrestrained and improperly restrained 9- to 12-year olds had significantly more open head, open upper extremity, and vascular injuries. When comparing injury types with age groups, upper extremity fractures, femoral fractures, dislocations, and spinal fractures were found to be significantly higher in older children.

Conclusions:

Preventing orthopaedic injuries in older children may be accomplished by changes in regulations or automotive safety equipment. Rear-facing child safety seats could possibly be improved to prevent head trauma in the youngest patients. There is a continued need to reinforce the importance of proper use of child safety devices to parents. Knowledge of the patient’s age, along with restraint status, might aid in diagnosis of less obvious MCV injuries.

Level of Evidence:

Level III.
The POSNA-COUR International Scholar Program. Results of the First 7 Years
Authors: Fornari Eric D. , Sabharwal Sanjeev , Schwend Richard M.
Published: January 2016

Background:

The Pediatric Orthopedic Society of North America (POSNA)-Children’s Orthopedics in Underserved Regions (COUR) International Scholar Program was initiated in 2007 to provide educational opportunities for emerging leaders who treat children with orthopaedic conditions in resource-challenged environments worldwide. Financial support is available each year for 4 to 6 orthopaedic surgeons to attend either the POSNA Annual Meeting or the International Pediatric Orthopedic Symposium. The scholars are also encouraged to visit selected centers for observerships during their trip. Since 2007 there have been 41 international scholars who have participated in the program. We wished to assess the impact of the program and to obtain feedback to improve the experience for future participants.

Methods:

A 23-question web-based survey was created and sent to 38 past scholars from 22 countries who have participated in the program by July 2013. The responses were gathered online and the data were analyzed for the 24 (62%) respondents from 18 countries who completed the survey.

Results:

Of the respondents, 16/24 (66%) reported that their current practice is comprised of at least 75% pediatrics. Twelve of 24 (52%) were fellowship trained in pediatric orthopaedics, typically outside of North America. All scholars found the meeting they attended to be very useful and have subsequently made changes to their clinical practice. Nineteen of 24 (82%) did a premeeting or postmeeting observership. Twenty-two of 24 (92%) participants have remained in contact with POSNA members they met at the meeting, with 86% of respondents stating that they have subsequently consulted POSNA members on management of patients. Sixty-two percent of the scholars had a POSNA member visit them following the scholarship and 29% have since returned to visit POSNA members for further clinical observerships. Twenty-one of 24 (91%) have had the opportunity to share the knowledge they gained with others in their region through lectures, surgical demonstrations, and/or clinical training. A common response from the scholars was that the scholarship program was a truly transformative life experience that provided them with an opportunity to receive the highest quality of professional education. The main challenges that these scholars report are lack of available fellowship/subspecialty training in their region, patients’ inability to pay, and excessive physician workload. All of the respondents expressed interest in arranging a POSNA cosponsored regional meeting.

Conclusions:

Since 2007, the POSNA-COUR international scholar program has been a fruitful resource for orthopaedists practicing in resource-challenged environments worldwide. It has provided unique training for the scholars and has further enabled them to teach others in their region. The program has thus far succeeded in fostering lasting relationships that have led to continued educational exchanges.

Level of Evidence:

Level IV—case series.
Breast Cancer is Common in Women With Ovarian Malignant Mixed Mullerian Tumors
Authors: Whynott Rachel M. , Manahan Kelly J. , Geisler John P.
Published: January 2016

Background:

Ovarian malignant mixed Mullerian tumors (MMMTs) are uncommon cancers. The purpose of the study was to determine the rate of metachronous or synchronous breast cancer as well as the rate of truncating germline BRCA1 and/or BRCA2 mutations in a series of women with these uncommon tumors.

Materials and Methods:

Records were reviewed to identify all women with MMMTs treated by the gynecologic oncology service. The stage, grade, histology, survival, and rate of coexistent breast cancer were determined. Tumor and/or peripheral blood was tested for BRCA1 and BRCA2 truncating mutations.

Results:

Twenty-four patients with MMMTs were found. Tumor and paired peripheral blood was available on 20 patients and 4 more patients had only peripheral blood available. Family pedigrees were available on all 24 patients. Fifteen of 24 (62.5%) patients were found to have metachronous or synchronous breast cancers with 9 of 15 (60%) having bilateral breast cancer. No BRCA1 or BRCA2 mutations were found (somatic or germline) in this cohort.

Conclusions:

Although an uncommon tumor, MMMTs are often found in women with breast cancer. Despite this finding, BRCA1 or BRCA2 germline mutations are not common in this population.

Precis:

Ovarian MMMTs are frequently found in women with cancer but are not frequently associated with defects in BRCA1 or BRCA2.
ACQUIRED VITELLIFORM DETACHMENT IN MULTIPLE MYELOMA
Authors: El Ameen Alaa , Mrejen-Uretsky Sarah , Abraham Julie , Souied Eric H. , Cohen Salomon Y.
Published: January 2016

Purpose:

To report a case of subfoveal acquired vitelliform detachment in a patient with multiple myeloma.

Methods:

Case report.

Results:

A 65-year-old man was referred for treatment of a serous macular detachment considered to be caused from chronic central serous chorioretinopathy or adult pseudovitelliform macular dystrophy. His medical history revealed an untreated multiple myeloma. Systemic chemotherapy was undertaken and resulted in a rapid resolution of the detachment.

Conclusion:

Multiple myeloma may be considered as a possible cause of vitelliform macular detachment.
Out-of-Hospital Cardiac Arrest in the Pediatric Population in Hong Kong
Authors: Law Alex Kwok-Keung , Ng Man-Ho , Hon Kam-Lun , Graham Colin A.
Published: January 2016

Aim

To describe the epidemiology and outcomes of out-of-hospital cardiac arrest (OHCA) in a Hong Kong (HK) pediatric population and to identify factors associated with favorable outcomes.

Methods

Retrospective case note review of patients younger than 18 years who presented to the emergency department of Prince of Wales Hospital, HK with cardiac arrest from 2003 to 2013. Patients were classified as infants (<1 year), children (1–11 years) and adolescents (12–18 years). Patient characteristics, OHCA details, interventions, and outcomes were reported following the Utstein format.

Results

There were 53 patients in the study (77.4% men) and 34.6% of patients had chronic illnesses. In the infant group, 35.7% had complicated pregnancies. The incidence of OHCA in HK was 5.37 per 100,000 person-years. Out-of-hospital cardiac arrest was identified by bystanders in 62.3%, but bystander cardiopulmonary resuscitation was provided in only 28.3%. Shockable rhythms were uncommon (9.4%). Most OHCA in infants had unknown causes. In children, commonest causes were respiratory illness and environmental hazards, and in adolescents, trauma and cardiogenic events. Overall survival to hospital discharge rate was 20.8%; 13.2% had good neurological outcomes. Bystander cardiopulmonary resuscitation (odds ratio [OR], 7.44; 95% confidence interval [95% CI], 1.75–31.7; P = 0.007), prehospital return of spontaneous circulation (OR, 11.4; 95% CI, 1.75–74.7; P = 0.013), and return of spontaneous circulation within 30 minutes (OR, 90.0; 95% CI, 11.1–727; P < 0.0005) were associated with survival to discharge.

Conclusions

The incidence of OHCA in HK is comparable to global data. The outcome of OHCA in the pediatric population has improved over the decades. Better prehospital care could improve outcome.
Lengthening Temporalis Myoplasty for Single-Stage Smile Reconstruction in Children with Facial Paralysis
Authors: Panossian Andre
Published: January 2016

Background:

Free muscle transfer for dynamic smile reanimation in facial paralysis is not always predictable with regard to cosmesis. Hospital stays range from 5 to 7 days. Prolonged operative times, longer hospital stays, and excessive cheek bulk are associated with free flap options. Lengthening temporalis myoplasty offers single-stage smile reanimation with theoretical advantages over free tissue transfer.

Methods:

From 2012 to 2014, 18 lengthening temporalis myoplasties were performed in 14 children for smile reconstruction. A retrospective chart review was completed for demographics, operative times, length of hospital stay, and perioperative complications.

Results:

Fourteen consecutive patients with complete facial paralysis were included. Four patients underwent single-stage bilateral reconstruction, and 10 underwent unilateral procedures. Diagnoses included Möbius syndrome (n = 5), posterior cranial fossa tumors (n = 4), posttraumatic (n = 2), hemifacial microsomia (n = 1), and idiopathic (n = 2). Average patient age was 10.1 years. Average operative time was 410 minutes (499 minutes for bilateral lengthening temporalis myoplasty and 373 for unilateral lengthening temporalis myoplasty). Average length of stay was 3.3 days (4.75 days for bilateral lengthening temporalis myoplasty and 2.8 for unilateral lengthening temporalis myoplasty). Nine patients required minor revisions.

Conclusions:

Lengthening temporalis myoplasty is a safe alternative to free tissue transfer for dynamic smile reconstruction in children with facial paralysis. Limited donor-site morbidity, shorter operative times, and shorter hospital stays are some benefits over free flap options. However, revisions are required frequently secondary to tendon avulsions and adhesions.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Sustaining Innovations in Complex Health Care Environments: A Multiple-Case Study of Rapid Response Teams
Authors: Stolldorf Deonni P. , Havens Donna S. , Jones Cheryl B.
Published: January 2016

Objectives

Rapid response teams (RRTs) are one innovation previously deployed in U.S. hospitals with the goal to improve the quality of care. Sustaining RRTs is important to achieve the desired implementation outcomes, reduce the risk of program investment losses, and prevent employee disillusionment and dissatisfaction. This study sought to examine factors that do and do not support the sustainability of RRTs.

Methods

The study was conceptually guided by an adapted version of the Planning Model of Sustainability. A multiple-case study was conducted using a purposive sample of 2 hospitals with high RRT sustainability scores and 2 hospitals with low RRT sustainability scores. Data collection methods included (a) a hospital questionnaire that was completed by a nurse administrator at each hospital; (b) semistructured interviews with leaders, RRT members, and those activating RRT calls; and (c) a review of internal documents. Quantitative data were analyzed using descriptive statistics; qualitative data were analyzed using content analysis.

Results

Few descriptive differences were found between hospitals. However, there were notable differences in the operationalization of certain factors between high- and low-sustainability hospitals. Additional sustainability factors other than those captured by the Planning Model of Sustainability were also identified.

Conclusions

The sustainability of RRTs is optimized through effective operationalization of organizational and project design and implementation factors. Two additional factors—individual and team characteristics—should be included in the Planning Model of Sustainability and considered as potential facilitators (or inhibitors) of RRT sustainability.
Factors Influencing Time-Dependent Quality Indicators for Patients With Suspected Acute Coronary Syndrome
Authors: France Daniel J. , Levin Scott , Ding Ru , Hemphill Robin , Han Jin , Russ Stephan , Aronsky Dominik , Weinger Matt
Published: January 2016

Objectives

Rapid risk stratification and timely treatment are critical to favorable outcomes for patients with acute coronary syndrome (ACS). Our objective was to identify patient and system factors that influence time-dependent quality indicators (QIs) for patients with unstable angina/non–ST elevation myocardial infarction (NSTEMI) in the emergency department (ED).

Methods

A retrospective, cohort study was conducted during a 42-month period of all patients 24 years or older suspected of having ACS as defined by receiving an electrocardiogram and at least 1 cardiac biomarker test. Cox regression was used to model the effects of patient characteristics, ancillary service use, staffing provisions, equipment availability, and ED and hospital crowding on ACS QIs.

Results

Emergency department adherence rates to national standards for electrocardiogram readout time and biomarker turnaround time were 42% and 37%, respectively. Cox regression models revealed that chief complaints without chest pain and the timing of stress testing and medication administration were associated with the most significant delays.

Conclusions

Patient and system factors both significantly influenced QI times in this cohort with unstable angina/NSTEMI. These results illustrate both the complexity of diagnosing patients with NSTEMI and the competing effects of clinical and system factors on patient flow through the ED.
Two Cultures in Modern Science and Technology: For Safety and Validity Does Medicine Have to Update?
Authors: Becker Robert E.
Published: January 2016

Two different scientific cultures go unreconciled in modern medicine. Each culture accepts that scientific knowledge and technologies are vulnerable to and easily invalidated by methods and conditions of acquisition, interpretation, and application. How these vulnerabilities are addressed separates the 2 cultures and potentially explains medicine's difficulties eradicating errors. A traditional culture, dominant in medicine, leaves error control in the hands of individual and group investigators and practitioners. A competing modern scientific culture accepts errors as inevitable, pernicious, and pervasive sources of adverse events throughout medical research and patient care too malignant for individuals or groups to control. Error risks to the validity of scientific knowledge and safety in patient care require systemwide programming able to support a culture in medicine grounded in tested, continually updated, widely promulgated, and uniformly implemented standards of practice for research and patient care. Experiences from successes in other sciences and industries strongly support the need for leadership from the Institute of Medicine's recommended Center for Patient Safely within the Federal Executive branch of government.
Multiphasic Dynamic Computed Tomography Evaluation of Liver Tissue Perfusion Characteristics Using the Dual Maximum Slope Model in Patients With Cirrhosis and Hepatocellular Carcinoma
Authors: Lee Dong Ho , Lee Jeong Min , Klotz Ernst , Han Joon Koo
Published: January 2016

Objective

The aim of this study was to investigate the feasibility of multiphasic dynamic computed tomography (CT) scans in providing liver tissue perfusion characteristics using the dual maximum slope model in patients with liver cirrhosis and hepatocellular carcinoma (HCC).

Materials and Methods

With institutional review board approval and acquisition of informed consent, we retrospectively analyzed the prospectively collected perfusion CT (PCT) data of 36 patients enrolled in a prospective clinical trial for pretherapeutic assessment of HCC. To obtain perfusion parameters including arterial liver perfusion (ALP), portal venous perfusion (PVP), and the hepatic perfusion index (HPI), 5-phase dynamic CT data sets with triple arterial phases including peak aortic and splenic enhancement information were selected from the PCT data sets. The PCT and 5-phase dynamic CT data sets extracted from the PCT data were analyzed using dedicated perfusion software based on the dual maximum slope model. Comparisons between the perfusion parameters of each method were performed using Wilcoxon signed rank test and intraclass correlation coefficients.

Results

The extraction of liver perfusion parameters from 5-phase dynamic CT scans was feasible using the dual maximum slope model, and no significant differences were observed between perfusion parameters obtained from 5-phase dynamic CT and from PCT in the liver parenchyma (ALP, P = 0.137; PVP, P = 0.110; HPI, P = 0.793) and in HCCs (ALP, P = 0.162; HPI, P = 0.131). Regarding intraclass correlation coefficients, excellent agreement was observed between perfusion parameters obtained using 5-phase dynamic CT and from PCT in both the liver parenchyma (ALP, 0.793; PVP, 0.831; HPI, 0.934) and in HCCs (ALP, 0.889; HPI, 0.943).

Conclusions

The extraction of liver perfusion parameters from 5-phase dynamic CT scans was feasible using the dual maximum slope model and provided comparable values to those obtained from PCT.
Catalyst design for enhanced sustainability through fundamental surface chemistry
Authors: Personick Michelle L. , Montemore Matthew M. , Kaxiras Efthimios , Madix Robert J. , Biener Juergen , Friend Cynthia M.
Published: January 2016

Decreasing energy consumption in the production of platform chemicals is necessary to improve the sustainability of the chemical industry, which is the largest consumer of delivered energy. The majority of industrial chemical transformations rely on catalysts, and therefore designing new materials that catalyse the production of important chemicals via more selective and energy-efficient processes is a promising pathway to reducing energy use by the chemical industry. Efficiently designing new catalysts benefits from an integrated approach involving fundamental experimental studies and theoretical modelling in addition to evaluation of materials under working catalytic conditions. In this review, we outline this approach in the context of a particular catalyst—nanoporous gold (npAu)—which is an unsupported, dilute AgAu alloy catalyst that is highly active for the selective oxidative transformation of alcohols. Fundamental surface science studies on Au single crystals and AgAu thin-film alloys in combination with theoretical modelling were used to identify the principles which define the reactivity of npAu and subsequently enabled prediction of new reactive pathways on this material. Specifically, weak van der Waals interactions are key to the selectivity of Au materials, including npAu. We also briefly describe other systems in which this integrated approach was applied.
Towards rational catalyst design: a general optimization framework
Authors: Wang Ziyun , Hu P.
Published: January 2016

Rational catalyst design is one of the most fundamental goals in heterogeneous catalysis. Herein, we briefly review our previous design work, and then introduce a general optimization framework, which converts catalyst design into an optimization problem. Furthermore, an example is given using the gradient ascent method to show how this framework can be used for rational catalyst design. This framework may be applied to other design schemes.