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Introduction: We aim to evaluate the association of early versus late venous thromboembolism (VTE) prophylaxis on in-hospital mortality among patients with severe blunt isolated traumatic brain injuries., Methods: Data from the American College of Surgeons Trauma Quality Program Participant Use File for 2017-2021 were analyzed. The target population included adult trauma patients with severe isolated traumatic brain injury (TBI). VTE prophylaxis types (low molecular weight heparin and unfractionated heparin) and their administration timing were analyzed in relation to in-hospital complications and mortality., Results: The study comprised 3609 patients, predominantly Caucasian males, with an average age of 48.5 y. Early VTE prophylaxis recipients were younger (P < 0.01) and more likely to receive unfractionated heparin (P < 0.01). VTE prophylaxis later than 24 h was associated with a higher average injury severity score and longer intensive care unit stays (P < 0.01). Logistic regression revealed that VTE prophylaxis later than 24 h was associated with significant reduction of in-hospital mortality by 38% (odds ratio 0.62, 95% confidence interval 0.40-0.94, P = 0.02). Additionally, low molecular weight heparin use was associated with decreased mortality odds by 30% (odds ratio 0.70, 95% confidence interval 0.55-0.89, P < 0.01)., Conclusions: VTE prophylaxis later than 24 h is associated with a reduced risk of in-hospital mortality in patients with severe isolated blunt TBI, as opposed to VTE prophylaxis within 24 h. These findings suggest the need for timely and appropriate VTE prophylaxis in TBI care, highlighting the critical need for a comprehensive assessment and further research concerning the safety and effectiveness of VTE prophylaxis in these patient populations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Although non-accidental trauma continues to be a leading cause of morbidity and mortality among children in the United States, the underlying factors leading to NAT are not well characterized. We aim to review reporting practices, clinical outcomes, and associated disparities among pediatric trauma patients experiencing NAT., Methods: A literature search utilizing PubMed, Google Scholar, EMBASE, ProQuest, and Cochrane was conducted from database inception until April 6, 2023. This review includes studies that assessed pediatric (age <18) trauma patients treated for NAT in the United States emergency departments. The evaluated outcome was in-hospital mortality rates stratified by race, age, sex, insurance status, and socioeconomic advantage., Results: The literature search yielded 2641 initial articles, and after screening and applying inclusion and exclusion criteria, 15 articles remained. African American pediatric trauma patients diagnosed with NAT had higher mortality odds than white patients, even when adjusting for comparable injury severity. Children older than 12 mo experienced higher mortality rates compared to those younger than 12 mo, although some studies did not find a significant association between age and mortality. Uninsured insurance status was associated with the highest mortality rate, followed by Medicaid and private insurance. No significant association between sex and mortality or socioeconomic advantage and mortality was observed., Conclusions: Findings showed higher in-hospital mortality among African American pediatric trauma patients experiencing child abuse, and in patients 12 mo or older. Medicaid and uninsured pediatric patients faced higher mortality odds from their abuse compared to privately insured patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This study aims to evaluate the association between trauma center type, verification level, and clinical outcomes in pediatric trauma patients with moderate and severe isolated blunt traumatic brain injury (TBI)., Methods: This is a retrospective cohort study utilizing the American College of Surgeons (ACS) Trauma Quality Program (TQP) Participant Use File (PUF) database from 2017 to 2021. Severely injured pediatric (<18 years) trauma patients with isolated moderate and severe TBI (AIS head >2, all other body regions <3) were included. Outcomes included in-hospital mortality, discharge disposition, intensive care unit length-of-stay (ICU-LOS), and ventilator-free days (VFDs)., Results: Patients treated at a level-I combined adult and pediatric trauma centers (CTCs) had significantly lower odds of in-hospital mortality than those treated at adult trauma centers (ATCs) (OR .495, 95% CI 0.291-.841, P = .009). Patients treated at level-I pediatric trauma centers (PTCs) (OR 2.726, 95% CI 2.059-3.609, P < .001) and level-II PTCs (OR 6.18, 95% CI 3.402-11.239, P < .001) were significantly more likely to be discharged home than equivalent-level ATCs., Conclusion: Pediatric patients with isolated blunt moderate and severe TBI treated at level-I PTCs and CTCs had reduced odds of in-hospital mortality compared to level-I ATCs. Patients at level I and II PTCs had significantly higher odds of discharge home than those at equivalent-level CTCs and ATCs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: We aim to evaluate the impact of recent changes in the residency matching process on surgical specialties' applicants and programs to offer recommendations on residency selection and matching processes., Methods: We utilized five databases while employing a Boolean query to search for studies from 2015 to March 2024. The search selection focused on factors and recent changes influencing residency match results across surgical specialties, including USMLE Step 1 pass/fail, research productivity, interview structure, and preference and geographic signaling., Results: The shift of the USMLE Step 1 to a pass/fail scoring system revealed a consensus among surgical program directors (PDs) and applicants not in favor of the change due to the emphasis on additional application elements. Research productivity was identified as a significant factor, especially in neurosurgery (with an average of 18.3 publications per applicant) and vascular surgery (8.3 publications), indicating a positive correlation between the number of publications and match outcomes. The adoption of virtual interviews has been well-received by both applicants and PDs, leading to an increase in the number of interviews offered and applicants. The implementation of preference and geographic signaling mechanisms has improved interview rates for applicants who utilize them., Conclusion: The transition to a pass/fail USMLE Step 1 has raised concerns among surgical specialties, necessitating a greater focus on Step 2 scores and research productivity. Virtual interviews and signaling have improved the accessibility and reach of the residency application process, however, the full impact of these changes on the perception of applicant-program fit remains unclear., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: This narrative review aims to evaluate the impact of current spinal immobilization practices on clinical outcomes in adult trauma patients with suspected or confirmed spinal injury to direct the creation of improved practice management guidelines., Methods: PubMed, ProQuest, Embase, Google Scholar, and Cochrane were searched for studies that evaluated the impact of spine immobilization practices during resuscitation in adult trauma patients and reported associated clinical outcomes. Outcomes included neurological deficits, in-hospital mortality, hospital length of stay (HLOS), ICU length of stay (ICU-LOS), discharge disposition, long-term functional status (modified Rankin scale), vascular injury rate, and respiratory injury rate., Results: Nine studies were included in this review, divided into two groups based on patient immobilization status. Patients compared with and without cervical immobilization had higher mortality, longer ICU-LOS, and a higher incidence of neurological deficits if immobilized. Immobilization only was associated with a higher incidence of indirect neurological injury and poor functional outcomes., Conclusion: Spinal immobilization during resuscitation in adult trauma patients is associated with a higher risk of neurological injury, in-hospital mortality, and longer ICU-LOS. Further research is needed to provide strong evidence for spinal immobilization guidelines and identify the optimal method and timing for immobilization practices in trauma patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with liver cirrhosis (LC) demonstrate significantly elevated mortality rates following a traumatic event. This study aims to examine and compare the clinical outcomes in adult trauma patients with pre-existing LC undergoing laparotomy or non-operative management (NOM). Additionally, the study aims to investigate various patient outcomes, including mortality rate based on transfusion needs and timing., Methods: This retrospective cohort study utilized the American College of Surgeons Trauma Quality Program Participant Use File (ACS-TQIP-PUF) 2017-21 to compare laparotomy vs NOM in adults (≥18 years) with pre-existing LC who presented to trauma facilities with isolated blunt solid organ abdominal injuries (Injury Severity Score ≥16, Abbreviated Injury Scale solid organ abdomen ≥3)., Results: Among 929 patients, 38.2% underwent laparotomy, while 61.7% received NOM. The in-hospital mortality rate was lower for patients who received NOM (52.3% vs 20.0%, P < .01). The risk of in-hospital mortality was significantly associated with laparotomy (OR 5.22, 95% CI: 2.06-13.18, P < .01) and sepsis (OR 99.50, 95% CI: 6.99-1415.28, P < .01). On average an increase in blood units in 4 hours was observed among those who experienced an in-hospital mortality (OR 5.65, 95% CI: 3.05-8.24, P < .01) and those who underwent laparotomy (OR 3.85, 95% CI: 1.36-6.34, P < .01)., Conclusion: Trauma patients with moderate to severe isolated organ injury and Liver cirrhosis had significantly higher mortality rates, acute renal failure, whole blood units received, as well as longer ICU-LOS when undergoing laparotomy compared to non-operative management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Disparities in venous thromboembolism (VTE) incidence and prophylaxis have been observed across racial groups. This study investigates the relationship between race, injury type, and the timing of VTE prophylaxis in severe trauma patients, both with and without isolated traumatic brain injuries. The primary goal is to analyze how these factors interact and their potential impact on clinical outcomes., Methods: A retrospective cohort study of the American College of Surgeons Trauma Quality Program Participant Use File (ACS-TQIP-PUF) from 2018 to 2021. Patient demographics, injury categories, VTE prophylaxis timing, injury severity, and in-hospital complications were collected. Multivariable regression models explored associations between race, injury type, VTE prophylaxis, and in-hospital mortality. Groups were analyzed by injury profile (isolated TBI vs non-TBI) and then by VTE prophylaxis timing (early ≤24 hours, late >24 hours)., Results: Of 68,504 trauma patients analyzed, the majority were non-Hispanic or Latino (83.3%), White (71.2%), and male (69.6%). Patients receiving late VTE prophylaxis had higher rates of DVT and PE across race groups than patients with early prophylaxis. Logistic regression showed Asian patients with TBI receiving early prophylaxis were significantly more likely to have in-hospital mortality (OR 16.27, CI = 1.11-237.43, P = .04) than other races., Conclusion: Patients who received late prophylaxis had higher VTE rates than early prophylaxis, independent of injury pattern or race. Additionally, assessing the implications of race in early VTE prophylaxis for isolated TBI showed that adult Asian patients had 16 times higher odds of in-hospital mortality compared to other races., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This systematic review aims to evaluate and compare differences in clinical outcomes for adult patients diagnosed with ISSPE who were managed with anticoagulation vs clinical surveillance., Methods: PubMed, Embase, ProQuest, Cochrane, and Google Scholar were searched to identify studies evaluating the use of anticoagulation and/or clinical surveillance in patients diagnosed with ISSPE. The search included studies published up to August 3, 2023. Outcomes of interest included 90-day recurrent venous thromboembolism (VTE), major bleeding, and all-cause mortality rates., Results: Ten studies were included with a total of 1224 patients. Of these patients, 791 were treated with anticoagulation and 433 underwent surveillance. Studies found no difference in recurrent VTE rates, with the majority of studies reporting no recurrence. Of the studies that reported VTE recurrence, rates were .5% to 1.4% for the anticoagulation groups and 3.1% to 3.2% for the surveillance groups. Major bleeding rates were also similar. In anticoagulated patients, major bleeding rates ranged from 1% to 10%. In clinical surveillance patients, the majority found no rate of major bleeding, with 2 studies reporting rates of .8% to 3.2%. Mortality rates ranged widely with no significant differences reported., Conclusion: Clinical surveillance appears to be a safe and effective alternative to anticoagulation in patients with ISSPE. Ninety-day rates of recurrent VTE, major bleeding, and mortality were comparable between groups. These findings highlight the need for updated practice management guidelines to improve patient outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Trauma-informed care (TIC) spans many different health care fields and is essential in promoting the well-being and recovery of traumatized individuals. This review aims to assess the efficacy of TIC frameworks in both educating providers and enhancing care for adult and pediatric patients., Methods: A literature search was conducted using PubMed, EMBASE, Proquest, Cochrane, and Google Scholar to identify relevant articles up to September 28, 2023. Studies implementing TIC frameworks in health care settings as a provider education tool or in patient care were included. Studies were further categorized based on adult or pediatric patient populations and relevant outcomes were extracted., Results: A total of 36 articles were included in this review, evaluating over 7843 providers and patients. When implemented as a provider education tool, TIC frameworks significantly improved provider knowledge, confidence, awareness, and attitudes toward TIC (P < 0.05 to P < 0.001). Trauma screenings and assessments also increased (P < 0.001). When these frameworks were applied in adult patient care, there were positive effects across a multitude of settings, including women's health, intimate partner violence, post-traumatic stress disorder, and inpatient mental health. Findings included reduced depression and anxiety (P < 0.05), increased trauma disclosures (5%-30%), and enhanced mental and physical health (P < 0.001)., Conclusions: This review underscores the multifaceted effectiveness of TIC frameworks, serving both as a valuable educational resource for providers and as a fundamental approach to patient care. Providers reported increased knowledge and comfort with core trauma principles. Patients were also found to derive benefits from these approaches in a variety of settings. These findings demonstrate the extensive applicability of TIC frameworks and highlight the need for a more comprehensive understanding of their applications and long-term effects., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This narrative review aims to evaluate the efficacy of adjunct direct peritoneal resuscitation (DPR) in the treatment of adult damage control surgery (DCS) patients both with and without hemorrhagic shock, and its impact on associated outcomes., Methods: PubMed, Google Scholar, EMBASE, ProQuest, and Cochrane were searched for relevant articles published through April 13th, 2023. Studies assessing the utilization of DPR in adult DCS patients were included. Outcomes included time to abdominal closure, intra-abdominal complications, in-hospital mortality, and ICU length of stay (ICU LOS)., Results: Five studies evaluating 437 patients were included. In patients with hemorrhagic shock, DPR was associated with reduced time to abdominal closure (DPR 4.1 days, control 5.9 days, p = 0.002), intra-abdominal complications including abscess formation (DPR 27 %, control 47 %, p = 0.04), and ICU LOS (DPR 8 days, control 11 days, p = 0.004). Findings in patients without hemorrhagic shock were conflicting. Closure times were decreased in one study (DPR 5.9 days, control 7.7 days, p < 0.02) and increased in another study (DPR 3.5 days, control 2.5 days, p = 0.02), intra-abdominal complications were decreased in one study (DPR 27 %, control 47 %, p = 0.04) and similar in another, and ICU LOS was decreased in one study (DPR 17 days, control 24 days, p < 0.002) and increased in another (DPR 13 days, control 11.4 days, p = 0.807)., Conclusion: In patients with hemorrhagic shock, adjunct DPR is associated with reduced time to abdominal closure, intra-abdominal complications such as abscesses, fistula, bleeding, anastomotic leak, and ICU LOS. Utilization of DPR in patients without hemorrhagic shock showed promising but inconsistent findings., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Limited research has assessed the effectiveness of Need for Trauma Intervention (NFTI) and Modified NFTI (MNFTI) criteria in accurately identifying triage rates in major trauma. We aim to evaluate the predictive capability of NFTI/MNFTI in determining rates of overtriage and undertriage, as well as associated outcomes., Methods: A literature search was conducted utilizing PubMed, Google Scholar, EMBASE, ProQuest, and Cochrane from conception to April 13th, 2023. Studies assessing the utilization of NFTI/MNFTI in identifying over and undertriage rates were included. Additional outcomes including mortality, ICU LOS, and resource allocation were evaluated. Outcomes were compared between NFTI/MNFTI and other triage metrics., Results: A total of 8 articles, including 175,650 trauma patients, were evaluated. NFTI utilization was associated with reduced overtriage rates compared to numerous tools including trauma triage matrix (TTM) and need for emergent intervention within 6 h (NEI-6) (NFTI 32.15%, TTM 44.5%, NEI-6 42.23%). Regarding undertriage, NFTI had lower rates than the secondary triage assessment tool (STAT) and TTM (NFTI 14.0%, STAT, 22.3%, TTM 14.3%) as well as Cribari Matrix Method (CMM) (NFTI .8%, CMM 7.6%, P < .0003). Additionally, the utilization of NFTI in combination with CMM yielded a significant reduction in undertriage rates compared to either tool alone (CMM/NFTI 2.7%, NFTI 4.6%, CMM 8.2%)., Conclusion: Implementation of NFTI/MNFTI resulted in more accurately capturing over and undertriage rates. Similar trends were identified when NFTI was used in combination with CMM. When compared to other triage tools, NFTI outperformed CMM, TTM, STAT, and NEI-6 in overtriage and/or undertriage rates., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Since the onset of the Covid-19 Pandemic, Telehealth utilization has grown rapidly; however, little is known about its efficacy in specific areas of healthcare, including trauma care in the emergency department. We aim to evaluate telehealth utilization in the care of adult trauma patients within United States emergency departments and associated outcomes over the past decade., Methods: PubMed, Google Scholar, EMBASE, ProQuest, and Cochrane were searched for relevant articles published from database conception to Dec 12th, 2022. Our review includes studies that assessed the utilization of telehealth practices within a United States emergency department for the treatment of adult (age ≥ 18) trauma patients. Evaluated outcomes included emergency department length of stay, transfer rates, cost incurred to patients and telehealthimplementing hospitals, patient satisfaction, and rates of left without being seen., Results: A total of 11 studies, evaluating 59,319 adult trauma patients, were included in this review. Telehealth practices resulted in comparable or reduced emergency department length of stay for trauma patients admitted to the emergency department. Costs incurred to the patient and rates of leaving without being seen were significantly reduced following telehealth implementation. There was no difference in transfer rates or patient satisfaction for telehealth practices compared to in-person treatment., Conclusion: Emergency department telehealth utilization significantly reduced trauma patient care-related costs, emergency department length of stay, and rates of leaving without being seen. No significant differences were found in patient transfer rates, patient satisfaction rates, or mortality rates following emergency department telehealth utilization., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To compare relative efficiency and chatter of high aspiration and vacuum settings., Design: In vitro laboratory study., Methods: The John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, was the study setting. Porcine nuclei were fixed in formalin and cut into 2.0 mm cubes. Lens cubes were phacoemulsified with Balanced tips at 50 and 60 mL/min aspiration with 500, 600, and 700 mm Hg vacuum with monitored forced infusion. Experiments were conducted at constant torsional power, longitudinal power, and intraocular pressure., Results: No significant change was observed in average chatter across each tested setting. Increasing aspiration rate did not increase efficiency. Increasing vacuum up to 600 mm Hg from 500 mm Hg did not change efficiency. However, increasing vacuum to 700 mm Hg decreased efficiency (p = 0.008 for 500 mm Hg vs 700 mm Hg and p = 0.05 for 600 mm Hg vs 700 mm Hg). Increasing aspiration and increasing vacuum did not significantly improve chatter., Conclusions: Increasing aspiration above 50 mL/min did not improve phacoemulsification efficiency. Increasing vacuum settings to 700 mm Hg decreases efficiency. Chatter did not significantly change with increasing aspiration and vacuum settings., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the optimum bottle height, vacuum, aspiration rate, and power settings in the peristaltic mode of the Whitestar Signature Pro machine with Ellips FX tip action (transversal)., Setting: John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA., Design: Experimental study., Methods: Porcine lens nuclei were hardened with formalin and cut into 2.0 mm cubes. Lens cubes were emulsified using transversal and fragment removal time (efficiency), and fragment bounces off the tip (chatter) were measured to determine optimum aspiration rate, bottle height, vacuum, and power settings in the peristaltic mode., Results: Efficiency increased in a linear fashion with increasing bottle height and vacuum. The most efficient aspiration rate was 50 mL/min, with 60 mL/min statistically similar. Increasing power increased efficiency up to 90% with increased chatter at 100%., Conclusion: The most efficient values for the settings tested were bottle height at 100 cm, vacuum at 600 mm Hg, aspiration rate of 50 or 60 mL/min, and power at 90%., (Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the psychometric properties of the VVSymQ(®) instrument, a new 5-item patient-reported outcome (PRO) measure for symptoms of varicose veins., Method: The VVSymQ(®) electronic daily diary was administered to outpatients who received routine treatment for varicose veins (N = 40). Compliance with diary administration and item score variability, reliability, construct validity, sensitivity to change, and clinically meaningful change were evaluated., Results: Patients completed >97 % of scheduled diary assessments (at screening, baseline, and week 8). The VVSymQ(®) instrument captured patients' pre-treatment symptoms (all VVSymQ(®) symptoms were endorsed by ≥75 % of patients at baseline), and the change post-treatment (mean change in score -6.1), with a large Cohen effect size (1.6). Test-retest reliability was high (intraclass correlation coefficient 0.96); internal consistency was good (Cronbach's alpha ≥0.76; baseline, week 8). VVSymQ(®) scores were more strongly associated with PRO scores that reflect symptoms and symptom impact (the Venous Insufficiency Epidemiological and Economic Study-Quality of Life/Symptoms [VEINES-QOL/Sym] instrument and the Chronic Venous Insufficiency Quality-of-Life Questionnaire [CIVIQ-20]) than with PRO scores that reflect appearance (the Patient Self-Assessment of Appearance of Visible Varicose Veins [PA-V(3)]) or clinician-reported outcome scores (the Clinical-Etiology-Anatomy-Pathophysiology [CEAP] Classification of Venous Disorders and Venous Clinical Severity Score [VCSS]), demonstrating construct validity. Patients reporting that symptoms were "moderately" or "much improved" on the Patient Global Impression of Change (PGIC) anchor (i.e., >97 % of patients) had mean improvements of -6.3 VVSymQ(®) points, while a cumulative distribution curve showed that 50 % of patients improved by ≥-5.8 points; thus, a score change of approximately -6 demonstrated a clinically meaningful change in this study. The clinically meaningful change in the VVSymQ(®) score was greater in patients with a greater baseline VVSymQ(®) symptom burden, and the VVSymQ(®) instrument captured clinically meaningful treatment benefit even in patients with a low baseline symptom burden., Conclusion: The 5-item VVSymQ(®) instrument is a brief, psychometrically sound, useful tool for evaluating patient-reported varicose veins symptoms.

Objective: To compare foam bubble size and bubble size distribution, stability, and degradation rate of commercially available polidocanol endovenous microfoam (Varithena®) and physician-compounded foams using a number of laboratory tests., Methods: Foam properties of polidocanol endovenous microfoam and physician-compounded foams were measured and compared using a glass-plate method and a Sympatec QICPIC image analysis method to measure bubble size and bubble size distribution, Turbiscan™ LAB for foam half time and drainage and a novel biomimetic vein model to measure foam stability. Physician-compounded foams composed of polidocanol and room air, CO2, or mixtures of oxygen and carbon dioxide (O2:CO2) were generated by different methods., Results: Polidocanol endovenous microfoam was found to have a narrow bubble size distribution with no large (>500 µm) bubbles. Physician-compounded foams made with the Tessari method had broader bubble size distribution and large bubbles, which have an impact on foam stability. Polidocanol endovenous microfoam had a lower degradation rate than any physician-compounded foams, including foams made using room air (p < 0.035). The same result was obtained at different liquid to gas ratios (1:4 and 1:7) for physician-compounded foams. In all tests performed, CO2 foams were the least stable and different O2:CO2 mixtures had intermediate performance. In the biomimetic vein model, polidocanol endovenous microfoam had the slowest degradation rate and longest calculated dwell time, which represents the length of time the foam is in contact with the vein, almost twice that of physician-compounded foams using room air and eight times better than physician-compounded foams prepared using equivalent gas mixes., Conclusion: Bubble size, bubble size distribution and stability of various sclerosing foam formulations show that polidocanol endovenous microfoam results in better overall performance compared with physician-compounded foams. Polidocanol endovenous microfoam offers better stability and cohesive properties in a biomimetic vein model compared to physician-compounded foams. Polidocanol endovenous microfoam, which is indicated in the United States for treatment of great saphenous vein system incompetence, provides clinicians with a consistent product with enhanced handling properties., (© The Author(s) 2015.)

We have recently reported on the development of a biomimetic vein model to measure the performance of sclerosing foams. In this study we employed the model to compare the commercially-available Varithena(®) (polidocanol injectable foam) 1% varicose vein treatment (referred to as polidocanol endovenous microfoam, or PEM) with physician compounded foams (PCFs) made using different foam generation methods (Double Syringe System and Tessari methods) and different foam formulations [liquid to gas ratios of 1:3 or 1:7; gas mixtures composed of 100% CO2, various CO2:O2 mixtures and room air (RA)]. PCFs produced using the DSS method had longer dwell times (DTs) (range 0.54-2.21 s/cm in the 4 mm diameter vein model) than those of the corresponding PCFs produced by the Tessari technique (range 0.29-0.94 s/cm). PEM had the longest DT indicating the best cohesive stability of any of the foams produced (2.92 s/cm). Other biomimetic model variables investigated included effect of vessel size, delayed injection and rate of plug formation (injection speed). When comparing the 4 and 10 mm vessel diameters, the DTs seen in the 10 mm vessel were higher than those observed for the 4 mm vessel, as the vein angle had been reduced to 5° to allow for foam plug formation. PCF foam performance was in the order RA > CO2:O2 (35:65) ≅ CO2:O2 (65:35) > CO2; PEM had a longer DT than all PCFs (22.10 s/cm) except that for RA made by DSS which was similar but more variable. The effect of delayed injection was also investigated and the DT for PEM remained the longest of all foams with the lowest percentage deviation with respect to the mean values, indicating a consistent foam performance. When considering rate of plug formation, PEM consistently produced the longest DTs and this was possible even at low plug expansion rates (mean 29.5 mm/s, minimum 20.9 mm/s). The developed vein model has therefore demonstrated that PEM consistently displays higher foam stability and cohesiveness when compared to PCFs, over a range of clinically-relevant operational variables.

Oxo(triphenylphosphine)[bis(3,5-di-tert-butyl-2-phenoxo)amido]rhenium(V) [(ONO(Cat))ReO(PPh3)] is prepared by the reaction of iododioxobis(triphenylphosphine)rhenium(V) [ReO2(PPh3)2I] with lead bis(3,5-di-tert-butyl-1,2-quinone-1-(2-oxy-3,5-di-tert-butylphenyl)imine) [Pb(ONO(Q))2]. In this reaction, the ONO ligand undergoes a two-electron reduction, with concomitant oxidation of PPh3 to OPPh3 and transformation of the dioxorhenium(V) fragment into a monooxorhenium(V) fragment, constituting a net nonclassical oxygen atom transfer. (ONO(Cat))ReO(PPh3) adopts a square pyramidal geometry with an apical oxo group [d(ReO) = 1.6873(14) Å] and a highly folded ONO ligand [O-Re-O = 129.55(6)°]. The fully reduced, trianionic oxidation state of the ONO ligand is confirmed by spectroscopic and metrical data.

A novel analysis system for the quantification of sclerosing foam properties under clinically relevant conditions was developed with the purpose of establishing a robust methodology for comparative characterisation of different foam formulations and production strategies. The developed biomimetic-inspired model comprised of 4 or 10 mm inner diameter polytetrafluoroethylene tubing, filled with a blood substitute and fixed to a platform with an adjustable inclination angle. Sclerosing foams were produced by mixing polidocanol with either atmospheric air or 100 % CO₂, using a double-syringe system method. Individual foams were injected into the tube, while videos were captured simultaneously. Videos were then transferred to an in-house computational foam analysis system (CFAS) which performed a sequence of semi-automated operations, allowing quantitative characterisation of sclerosing foam dynamic behaviour. Using CFAS, degradation rates of different foams were measured and the effect of gas composition, liquid sclerosant concentration and time delay between foam production and injection were evaluated.

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.

Background: Foam generated by manual agitation of liquid sclerosant with air or gas is routinely utilized to treat refluxing veins. Although generally well tolerated, serious neurological events have been reported. The composition and properties of the foam, including bubble size and gaseous components, may contribute to the potential for microcirculatory obstruction and cerebral ischemia. We tested an ultra-low nitrogen polidocanol endovenous microfoam with controlled bubble size and density and hypothesized that patients at risk due to the presence of middle cerebral artery (MCA) bubble emboli during microfoam injection would not demonstrate evidence of clinical or subclinical cerebral infarction., Methods: Patients with great saphenous vein incompetence were treated with ultra-low nitrogen (≤ 0.8%) polidocanol endovenous microfoam injected under ultrasound guidance. Patients with right-to-left shunt were included to evaluate the safety of cerebral arterial bubbles. All patients with MCA emboli detected by transcranial Doppler during endovenous microfoam ablation received intensive surveillance for microinfarction, including brain magnetic resonance imaging and measurement of cardiac troponin-I., Results: MCA bubble emboli were detected in 60 of 82 treated patients; 22 patients had no detectable emboli. Among patients with MCA bubbles detected, 49 (82%) had ≤ 15 bubbles. No patients developed magnetic resonance imaging abnormalities, neurological signs, or elevated cardiac troponin., Conclusions: Patients treated with foamed liquid sclerosants are commonly exposed to cerebrovascular gas bubbles. In this series of 60 high-risk patients with MCA bubble emboli during or after treatment with ultra-low nitrogen polidocanol endovenous microfoam, there was no evidence of cerebral or cardiac microinfarction. The results of this study cannot be generalized to foams compounded using bedside methodologies, since the composition of these foams is substantially different., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Foam sclerotherapy is not a defined procedure nor is the product uniform or licensed for use but it is now accepted practice in most territories worldwide. Foam sclerotherapy has been used to treat a wide range of venous conditions from the closure of incompetent great saphenous trunk veins to telangiectasia and from venous malformations to hemorrhoids with good outcomes being reported. There is a rapidly expanding body of literature supporting its safety and efficacy as well as a few case histories of serious complications. This article will focus on the current role of foam sclerotherapy in the treatment of varicose veins., (Copyright 2010. Published by Elsevier Inc.)

Background: Varicose veins are common and increasingly are being treated by less invasive endoscopic methods such as foam sclerotherapy. Patent foramen ovale (PFO) is also common, present in approximately one-quarter of adults. PFO allows bubbles introduced by foam sclerotherapy to cross into the general circulation, potentially causing cerebral artery gas embolization with unevaluated consequences., Methods: Men and women aged 18 to 60 years with symptomatic varicose veins (CEAP C(3-5)) responded to an advertisement to recruit volunteers for a study on endovenous microfoam ablation (EMA). Participants' veins were screened by duplex ultrasound imaging, and those with isolated great saphenous vein (GSV) incompetence were tested for right-to-left (R-L) vascular shunt using transcranial Doppler (TCD) of the middle cerebral artery to detect the presence of bubble emboli after an injection of an agitated saline, blood, and air mixture as a contrast at rest and with the Valsalva maneuver., Results: Of 221 participants tested for R-L shunt, 85 (38.5%) were positive at rest (95% confidence interval [CI], 32.5-45.2) and 114 (51.8%) were positive after the Valsalva maneuver (95% CI, 45.4-58.5). A total 130 patients (58.8%) were positive for R-L shunt at rest or after Valsalva (95% CI, 52.5%-65.1%). This is significantly higher than the reported 26% prevalence of PFO in the general population (95% CI, 24.4-30.1)., Conclusions: The prevalence of R-L shunt in patients with GSV incompetence CEAP C(3-5) in this study was higher than expected in the general population. TCD does not differentiate between intracardiac shunts and intrapulmonary shunts, so this observation needs further investigation. This link between R-L shunt and varicose veins is novel and, whether etiologic or functional, may improve the understanding of both conditions. The findings have importance in the treatment of varicose veins with foam sclerotherapy and EMA., (Copyright 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Introduction: Most leg ulcers are caused by venous disease, the most common cause of venous hypertension being superficial vein incompetence. The ESCHAR trial tested the value of superficial vein surgery combined with compression in the healing and recurrence of venous leg ulcers compared with compression alone., Methods: A total of 500 patients with chronic venous leg ulcers, or recently healed ulcers, were randomized to superficial vein surgery and compression or compression alone. Vein surgery was saphenofemoral ligation and great saphenous stripping and phlebectomy or saphenopopliteal ligation and phlebectomy., Results: Ulcer healing was virtually identical between the 2 groups at 65% at 24 weeks; subgroup analysis failed to show a benefit for surgery to promote ulcer healing. Ulcer recurrence rate was halved in those that underwent surgery regardless of the presence of deep vein incompetence., Conclusion: Superficial vein surgery should be considered in all leg ulcer sufferers to reduce ulcer recurrence rather than accelerate ulcer healing.

Multiple hamartoma syndrome (also known as Cowden's syndrome) is a genetic disorder. The signs and symptoms of this disorder often do not appear concurrently or with the same degree of severity. While much of the literature regarding Cowden's syndrome (CS) focuses on the dermatologic and gastro-enterologic features of the disease, there also are unique oral and facial symptoms that manifest early in this condition. This disorder might be overlooked and underdiagnosed by the dental community. There is a strong link between CS and female breast cancer, thyroid cancer, gastrological polyps, and rare forms of brain cancer; as a result, it is essential for the dental community to gain a greater understanding of this syndrome and its unique oral manifestations.

Brittle failure of bone cement remains a problem for the long-term stability of hip prostheses. Fibers have been developed from poly(methyl methacrylate) (PMMA) that retain the chemistry of bone cement, but improve the mechanical properties greatly. To fabricate the fibers, a polymer melt is extruded out of a small die (spinneret) and pulled onto a take-up wheel. Varying the speed of extrusion and temperature of the melt can control the viscosity of the molten polymer. This study examines the effect of melt viscosity on the resultant properties of fibers fabricated from PMMA. The goals are to optimize fiber processing and determine processing-structure--property relationships. Resultant fibers had moderate to high levels of retained molecular orientation, and ultimate tensile strengths (UTS) ranging from 60 to 225 MPa, moduli from 1.5 to 3.5 GPa, and strain to failure from 10 to 40%. Fibers fabricated at a constant viscosity and draw velocity had identical properties, whereas decreasing the viscosity generally increased the mechanical properties and retained orientation. Linear regression models were constructed to predict how the processing variables affect the structure (orientation) of the fiber and how the structure affects the UTS. This can be used to design efficient processing methods for PMMA fibers., (Copyright 2002 John Wiley & Sons, Inc.)

A novel material, self-reinforced composite poly(methyl methacrylate) (SRC-PMMA) has been previously developed in this laboratory. It consists of high-strength PMMA fibers embedded in a matrix of PMMA derived from the fibers. As a composite material, uniaxial SRC-PMMA has been shown to have greatly improved flexural, tensile, fracture toughness and fatigue properties when compared to unreinforced PMMA. Previous work examined one empirically defined processing condition. This work systematically examines the effect of processing time and temperature on the thermal properties, fracture toughness and fracture morphology of SRC-PMMA produced by a hot compaction method. Differential scanning calorimetry (DSC) shows that composites containing high amounts of retained molecular orientation exhibit both endothermic and exothermic peaks which depend on processing times and temperatures. An exothermic release of energy just above Tg is related to the release of retained molecular orientation in the composites. This release of energy decreases linearly with increasing processing temperature or time for the range investigated. Fracture toughness results show a maximum fracture toughness of 3.18 MPa m1/2 for samples processed for 65 min at 128 degrees C. Optimal structure and fracture toughness are obtained in composites which have maximum interfiber bonding and minimal loss of molecular orientation. Composite fracture mechanisms are highly dependent on processing. Low processing times and temperatures result in more interfiber/matrix fracture, while higher processing times and temperatures result in higher ductility and more transfiber fracture. Excessive processing times result in brittle failure., (Copyright 1999 Kluwer Academic Publishers)

Total joint prostheses are often fixed in the bone using bone cement. The cement mantle, however, is prone to fatigue fracture that can lead to failure of the mantle, evolution of bone cement particles, and eventual loosening and failure of the prosthesis. A new material, self-reinforced composite poly(methyl methacrylate) (SRC-PMMA) was developed previously by the authors. This material has a similar chemical composition to bone cement, with the matrix and reinforcing fibers both fabricated from PMMA. One potential use for this material is as a precoat for hip prostheses or other stemmed prostheses. This study sought to examine the strength of the bonds that SRC-PMMA forms with simulated prostheses and bone cement. SRC-PMMA was woven about Co-Cr rods and push out tests were performed. Samples were tested in air as processed or after immersion in saline for 30 days at 37 degrees C. Three different weaves were investigated and compared to bone cement. Bone cement and SRC-PMMA formed interfacial bonds with Co-Cr rods that failed at an average load (stress) of 980 N (2.0 MPa). After saline immersion, the bone cement's interfacial bond strength was 642 N (1.23 MPa) and the tight weave SRC-PMMA was statistically stronger at 973 N (1.86 MPa). The shear strength within bone cement alone as measured by push out tests was an order of magnitude higher at 9210 N (15.2 MPa) in air and 9900 N (15.7 MPa) after saline immersion. The bond between SRC-PMMA and bone cement was 10,900 N (17.9 MPa) in air and 9610 N (15.8 MPa) after immersion in saline. Woven SRC-PMMA performed as well or better than bone cement in these push out tests.

Loosening remains an impediment to the long-term success of total hip replacements despite numerous improvements in the materials used. In cemented prostheses, fatigue and fracture of bone cement have been implicated in the failure of these devices. A new material, self-reinforced composite poly(methyl methacrylate). (SRC-PMMA), has been developed. SRC-PMMA is formed by a novel processing method that will be described. The composite consists of high strength, highly oriented PMMA fibers embedded in a matrix of PMMA. Using a woven form of SRC-PMMA, an in vitro physical and mechanical evaluation was performed to assess the feasibility of its use in an orthopedic prosthesis. Three different weaves of SRC-PMMA were evaluated in bending and fracture toughness in air, after immersion for 30 days in 37 degrees C saline, and after gamma irradiation followed by immersion. Bending modulus and strength were decreased by gamma irradiation followed by saline immersion. The effect of saline immersion alone on bending strength and modulus was negligible. Saline immersion and gamma irradiation followed by saline immersion was shown to have little or no effect on the fracture toughness of woven SRC-PMMA. Differences in the fracture processes of the different weaves were found and can be related to the differing orientation of fibers to the fracture toughness pre-crack. Optimally incorporated SRC-PMMA absorbs the same amount of water as bone cement. Comparison to previous and current work with bone cement controls shows that SRC-PMMA is a material equal to or better than bone cement in all tests performed. It deserves further consideration as a candidate biomaterial.

A reciprocal connection is known to exist between the cuneate nucleus, which is a first-order somatosensory nucleus, and the cochlear nucleus, which is a first-order auditory nucleus. We continued this line of study by investigating the fiber endings of this projection in the cochlear nucleus of rats using the neuronal tracer Phaseolus vulgaris leucoagglutinin in combination with ultrastructural and immunocytochemical analyses. In the cochlear nucleus, mossy fiber terminals had been described and named for their morphologic similarity to those in the cerebellum, but their origins had not been discovered. In the present study, we determined that the axonal projections from the cuneate region gave rise to mossy fiber terminals in the granule cell regions of the ipsilateral cochlear nucleus. The cuneate mossy fibers appear to be excitatory in nature, because they are filled with round synaptic vesicles, they make asymmetric synapses with postsynaptic targets, and they are labeled with an antibody to glutamate. The postsynaptic targets of the mossy fibers include dendrites of granule cells. This projection onto the granule cell interneuron circuit of the cochlear nucleus indicates that somatosensory cues are intimately involved with information processing at this early stage of the auditory system.

We demonstrate that the metabotropic glutamate receptor mGluR1 alpha is enriched in two interneuron cell populations in the dorsal division of the cochlear nucleus. Electron microscopic analysis confirms that mGluR1 alpha immunoreactivity is concentrated in the dendritic spines of cartwheel cells and in dendrites of the recently described unipolar brush cells. The cartwheel cells, which have many similarities to the Purkinje cells of the cerebellum, participate in a local neuronal circuit that modulates the output of the dorsal cochlear nucleus. Immunostained unipolar brush cells were observed in granule cell regions of the cochlear nucleus and the vestibulocerebellum. The presence of analogous cell types with similar patterns of immunolabeling in the cerebellum and in the dorsal cochlear nucleus suggests that a shared but as yet unknown mode of processing may occur in both structures.

The t(1;19) chromosomal translocation of pediatric pre-B cell lymphoblastic leukemia produces the E2A-PBX1 oncogene, which can transform fibroblasts, induce acute myeloid leukemia and T cell lymphomas in mice, and immortalize factor-dependent myeloid progenitors in cultured marrow. The homeodomain of Pbx1 binds ATCAATCAA, and while Pbx1 does not activate transcription through this motif, E2A-Pbx1 induces constitutive transactivation. Here, we investigate whether DNA-binding by Pbx1 or transcriptional activation by E2A are essential for the transforming abilities of E2A-Pbx1. Elimination of DNA-binding in E2A-Pbx1 by point mutations in the Pbx1 homeodomain or by large deletions that removed the Pbx1 homeodomain and carboxyl terminus did not alter ability of E2A-Pbx1 to induce focus-formation in fibroblast, even though these mutations completely eliminated its ability to activate transcription through the PRS. These same DNA-binding mutations, however, severely impaired or eliminated the ability of E2A-Pbx1 to immortalize factor-dependent myeloid progenitors in marrow cultures. Elimination of the first transcriptional activation domain of E2A abolished both fibroblast and myeloid transforming activities while elimination of the second altered neither of these activities. We conclude that DNA-binding is important for the ability of E2A-Pbx1 to disrupt differentiation, as evidenced in myeloblast immortalization, but dispensable for its ability to induce focus-formation, and that the aminoterminal domain of E2A, which strongly activates transcription, is essential for both transforming activities.

An Er:YAG laser coupled with a cooling stream of water effectively removes dental hard tissues. However, before such a system can be deemed clinically viable, some safety and efficacy issues must be addressed. We compared the bonding of composite to dentin following the preparation of the dentinal surface with either an Er:YAG laser (lambda = 2.94 microns) or a standard dental bur and with and without a subsequent acid-etching treatment. The crowns of extracted human molars were removed, revealing the underlying dentin. We removed an additional thickness of material with either a dental handpiece or an Er:YAG laser (350 mJ/pulse at 6 Hz) by raster-scanning the samples under a fixed handpiece or laser. Comparable surface roughnesses were obtained. Several samples from each group received an acid-conditioning treatment. A cylinder of composite was bonded onto the prepared surfaces. The dentin-composite bond was then shear-stressed to failure on a universal testing apparatus. The results indicate that laser-irradiated samples had improved bond strengths compared with acid-etched and handpiece controls. SEM photographs of the surfaces show exposed tubules following the laser treatment: tubules could also be exposed with acid etching. We conclude that Er:YAG laser preparation of dentin leaves a suitable surface for strong bonding or an applied composite material.

In the cochlear nucleus of mammals, the relatively homogeneous responses of auditory nerve fibers are transformed into a variety of different response patterns by the different classes of resident neurons. The spectrum of these responses is hypothesized to depend on the types and distribution of receptors, ion channels, G proteins, and second messengers that form the signaling capabilities in each cell class. In the present study, we examined the immunocytochemical distribution of the inositol 1,4,5-triphosphate (IP3) receptor in the dorsal cochlear nucleus to better understand how this second messenger might be involved in shaping the neural signals evoked by sound. Affinity-purified polyclonal antibodies directed against the IP3 receptor labeled a homogeneous population of neurons in the dorsal cochlear nucleus of rats, guinea pigs, mustache bats, cats, New World owl monkeys, rhesus monkeys, and humans. These cells were all darkly immunostained except in the human where the labeling was less intense. Immunoblots of dorsal cochlear nucleus tissue from the rat revealed a single band of protein of molecular weight approximately 260 kD, which is the same size as the purified receptor, indicating that our antibodies reacted specifically with the IP3 receptor. These immunolabeled neurons were identified as cartwheel cells on the basis of shared characteristics across species, including cell body size and distribution, the presence of a highly invaginated nucleus, and a well-developed system of cisternae. Reaction product was localized along the membranes of rough and smooth endoplasmic reticulum, subsurface cisternae, and the nuclear envelope. This label was distributed throughout the cartwheel cell body and dendritic shafts but not within dendritic spines, axons, or axons terminals. The regular pattern of immunolabeling across mammals suggests that IP3 and cartwheel cells are conserved in evolution and that both play an important but as yet unknown role in hearing.

E2A-PBX1 is the oncogene produced at the t(1;19) chromosomal breakpoint of pediatric pre-B-cell leukemia. Expression of E2A-Pbx1 induces fibroblast transformation and myeloid and T-cell leukemia in mice and arrests differentiation of granulocyte macrophage colony-stimulating factor-dependent myeloblasts in cultured marrow. Recently, the Drosophila melanogaster protein Exd, which is highly related to Pbx1, was shown to bind DNA cooperatively with the Drosophila homeodomain proteins Ubx and Abd-A. Here, we demonstrate that the normal Pbx1 homeodomain protein, as well as its oncogenic derivative, E2A-Pbx1, binds the DNA sequence ATCAATCAA cooperatively with the murine Hox-A5, Hox-B7, Hox-B8, and Hox-C8 homeodomain proteins, which are themselves known oncoproteins, as well as with the Hox-D4 homeodomain protein. Cooperative binding to ATCAATCAA required the homeodomain-dependent DNA-binding activities of both Pbx1 and the Hox partner. In cotransfection assays, Hox-B8 suppressed transactivation by E2A-Pbx1. These results suggest that (i) Pbx1 may participate in the normal regulation of Hox target gene transcription in vivo and therein contribute to aspects of anterior-posterior patterning and structural development in vertebrates, (ii) that E2A-Pbx1 could abrogate normal differentiation by altering the transcriptional regulation of Hox target genes in conjunction with Hox proteins, and (iii) that the oncogenic mechanism of certain Hox proteins may require their physical interaction with Pbx1 as a cooperating, DNA-binding partner.

The organization of neurons and fibers in the cochlear nuclei of the alligator lizard (Gerrhonotus multicarinatus) was examined with light and electron microscopy. In this species, much is known about the anatomy and physiology of the inner ear including the cochlear nerve, but little is known about the synaptic connections of cochlear fibers on second-order neurons. These data will help to develop general principles addressing the cellular organization of the vertebrate auditory system. Subdivisions of the cochlear nuclei were defined on the basis of their histologic appearance and neuronal composition. Neuron classes were proposed from their light microscopic and ultrastructural features. Nucleus magnocellularis medialis consists of a homogeneous population of neurons called "lesser ovoid" cells. Nucleus magnocellularis lateralis consists of "greater ovoid" and "small" cells. Nucleus angularis lateralis consists of "spindle" cells. Lastly, nucleus angularis medialis contains a population of large neurons called "duckhead" and "multipolar" cells, and a population of smaller neurons called "bulb" and "agranular" cells. These neuron populations are differentially innervated by tectorial and free-standing cochlear fibers that are associated with separate frequency ranges. All neuronal populations except agranular cells were observed to receive synaptic input from cochlear nerve fibers. In nucleus magnocellularis medialis and nucleus angularis medialis, primary afferents form both chemical and electrical synapses with resident neurons. These observations imply that acoustic information is synaptically processed in fundamentally distinct ways in the cochlear nuclei of alligator lizards and distributed along separate neural circuits. Thus, the characteristic structural and functional dichotomy of the alligator lizard inner ear is extended to central auditory pathways by way of cochlear nerve projections.

E2A-PBX1 is a chimeric homeobox oncogene formed by the t(1;19) translocation of human pre-B cell acute lymphoblastic leukemia (ALL). In a previous study, we found that retroviral expression of E2A-Pbx1 in the marrow of reconstituted mice induced the formation of acute myeloid leukemia (AML) in vivo. Here, we report that E2A-Pbx1 can also immortalize myeloid progenitors in vitro, and that the outgrowth of immortalized myeloblasts is evident only in the presence of the myeloid lymphokine, granulocyte-macrophage colony stimulating factor (GM-CSF). When cultured in the presence of GM-CSF, responsive myeloblasts from normal marrow exhibit concurrent proliferation and differentiation, and undergo terminal differentiation into non-mitotic neutrophils and macrophages within 4 weeks. Infection of identical cultures with a retrovirus encoding E2A-Pbx1 produces a rapid outgrowth of myeloid progenitors that express high levels of E2A-Pbx1 protein. A small fraction of myeloblasts in each population exhibited limited differentiation to neutrophils, and all populations of myeloblasts retained a strict dependence on GM-CSF for both survival and proliferation. This data suggests that the function of E2A-Pbx1 in leukemias is to strongly retard differentiation without affecting growth-factor dependence.

Intracellular recordings from the dorsal cochlear nucleus have identified cells with both simple and complex action potential waveforms. We investigated the hypothesis that cartwheel cells are a specific cell type that generates complex action potentials, based on their analogous anatomical, developmental, and biochemical similarities to cerebellar Purkinje cells, which are known to discharge complex action potentials. Intracellular recordings were made from a brain slice preparation of the guinea pig dorsal cochlear nucleus. A subpopulation of cells discharged a series of two or three action potentials riding on a slow depolarization as an all-or-none event; this discharge pattern is called a complex spike or burst. These cells also exhibited anodal break bursts, anomalous rectification, subthreshold inward rectification, and frequent inhibitory postsynaptic potentials (IPSPs). Seven complex-spiking cells were stained with intracellular dyes and subsequently identified as cartwheel neurons. In contrast, six identified simple-spiking cells recorded in concurrent experiments were pyramidal cells. The cartwheel cell bodies reside in the lower part of layer 1 and the upper part of layer 2 of the nucleus. The cells are characterized by spiny dendrites penetrating the molecular layer, a lack of basal dendritic processes, and an axonal plexus invading layers 2 and 3, and the inner regions of layer 1. The cartwheel cell axons made putative synaptic contacts at the light microscopic level with pyramidal cells and small cells, including stellate cells, granule cells, and other cartwheel cells in layers 1 and 2. The axonal plexus of individual cartwheel cells suggests that they can inhibit cells receiving input from either the same or adjacent parallel fibers and that this inhibition is distributed along the isofrequency contours of the nucleus.

E2A-PBX1 is a chimeric gene formed by the t(1;19)(q23;p13.3) chromosomal translocation of pediatric pre-B-cell leukemia. The E2A-Pbx1 fusion protein contains sequences encoding the transactivation domain of E2A joined to a majority of the Pbx1 protein, which contains a novel homeodomain. Earlier, we found that expression of E2A-Pbx1 causes malignant transformation of NIH 3T3 fibroblasts and induces myeloid leukemia in mice. Here we demonstrate that the homeodomains encoded by PBX1, as well as by the highly related PBX2 and PBX3 genes, bind the DNA sequence ATCAATCAA. E2A-Pbx1 strongly activates transcription in vivo through this motif, while Pbx1 does not. This finding suggests that E2A-Pbx1 transforms cells by constitutively activating transcription of genes regulated by Pbx1 or by other members of the Pbx protein family.

The tyrosine protein kinase p56lck transduces signals important for antigen-induced T-cell activation. In transgenic mice, p56lck is oncogenic when overexpressed or expressed as a mutant, catalytically activated enzyme. In humans, the LCK gene is located at the breakpoint of the t(1;7)(p34;q34) chromosomal translocation. This translocation positions the beta T-cell receptor constant region enhancer upstream of the LCK gene without interrupting the LCK coding sequences, and a translocation of this sort occurs in both the HSB2 and the SUP-T-12 T-cell lines. We have found that, although the level of the p56lck protein in HSB2 cells is elevated approximately 2-fold in comparison with that in normal T-cell lines, total cellular tyrosine protein phosphorylation is elevated approximately 10-fold. Increased levels of phosphotyrosine in HSB2 cells resulted from mutations in the LCK gene that activated its function as a phosphotransferase and converted it into a dominant transforming oncogene. The oncogenic p56lck in HSB2 cells contained one amino acid substitution within the CD4/CD8-binding domain, two substitutions in the kinase domain, and an insertion of Gln-Lys-Pro (QKP) between the SH2 and kinase domains. In NIH 3T3 fibroblasts, three of these mutations cooperated to produce the fully oncogenic form of this p56lck variant. These results suggest that mutation of LCK may contribute to some human T-cell leukemias.

Conclusion: The question of why there is a need to be aware of the theoretical principles of prevention and prevention programs raises several responses. First, there appears to be higher incidents of inadequate responses to the transitions of life, normative and otherwise, as indicated by the scope of the projects presented in the video. Instead of alleviating the frustration and stress associated with change, and thereby reducing the incidence of disorders within the community, inadequate coping mechanisms exacerbate the impact of the change on the individual. Therefore, programs which develop social skills that alleviate the impact of stressors on the individual will reduce the overall impact of disorders in the community.Second, there has been a general decrease in the number of services which adequately address health related needs on the federal, state, local, and private levels. For those who are in need of service, this lack of availability compounded with the lack of community, relegates the individual to a life of isolation. A core theme that emerged from the video was when individuals are isolated from the community there is a higher occurrence of poor coping mechanisms in response to stressors.Third, as general health care moves towards the 21st century, managed health care systems are becoming the mode of accepted treatment. In an attempt to keep the cost of health care reasonable, many facilities are encouraging their participants to seek resolution to problems before they become detrimental to the overall well being of the participants.Lastly, as professional in the fields of psychology, sociology, and public policy, it is imperative that a thorough understanding of the ideological principles of prevention and prevention programs are presented to ensure the development of programs which adequately meet the needs of future societies.

Sensory epithelia are often spatially reiterated throughout their representation in the central nervous system. Differential expression of this representation can reveal specializations of the organism's behavioral repertoire. For example, the nature of the central representation of sound frequency in the auditory system has provided important clues in understanding ecological pressures for acoustic processing. In this context, we used electrophysiological techniques to map the frequency organization of the dorsal cochlear nucleus in nine cats. Frequency responses were sampled in increments of 100-200 microns along electrode tracks that entered the dorsomedial border of the nucleus and exited at the ventrolateral border. Electrode tracks were oriented parallel to the long (or strial) axis of the nucleus so that each penetration sampled neural responses for most of the cat's audible frequencies and remained in or near the pyramidal cell layer for several millimeters. Nearly identical distance versus frequency relationships were obtained for different rostral-caudal locations within the same cat as well as for different cats. Frequency responses systematically decreased from above 50 kHz at the most dorsomedial locations in the nucleus to below 1 kHz in the most ventrolateral regions. The rate of frequency change was roughly three times greater in high frequency regions than in low frequency regions. In addition, the highest pyramidal cell density and longest rostral-caudal axis was observed for the middle third of the dorsal-ventral axis of the nucleus. As a result, roughly half of all pyramidal cells responded to frequencies between 8-30 kHz. The representation of neural tissue for these frequencies may be related to the importance of spectral cues in sound locations.

Although pharmacological stimulation of a wide variety of transmitter receptors triggers phosphoinositide (PI) turnover, little is known about the type of synaptic activity required to activate this system. To investigate this question, we have used primary cultures of embryonic cortical neurons, which develop functional glutamate and GABA synapses during maturation in vitro. Mature cultures display spontaneous synaptic activity that is totally suppressed by tetrodotoxin (TTX). PI turnover, assayed by the lithium-sensitive accumulation of [3H]CDP-diacylglycerol, was readily detected under basal conditions and was abolished by TTX. Increased excitatory synaptic activity induced by picrotoxin, an antagonist of GABAA receptor-mediated inhibition, further stimulated PI turnover. Similar results were obtained when PI turnover was assayed using [3H]inositol labeling. With either assay, the magnitude of synaptically induced PI turnover was comparable to maximal responses produced by muscarinic receptor stimulation. Although a component of the spontaneous synaptic currents is sensitive to N-methyl-D-aspartate (NMDA)-preferring glutamate receptor antagonists, blockade of NMDA receptors did not affect PI turnover associated with synaptic transmission. To assess the time course of synaptically mediated PI turnover, the amplitude and duration of spontaneous synaptic currents were reduced by lowering the extracellular Ca2+ concentration from 2.25 to 0.5 mM, a maneuver that suppresses basal PI turnover. Increases in PI turnover were detected as early as 5 min following restoration of the extracellular Ca2+ concentration to 2.25 mM. Taken together, these findings indicate that activation of the PI system is associated with physiological levels of glutamatergic synaptic transmission.