Exposure Effects of Environmentally Relevant Concentrations of the Tricyclic Antidepressant Amitriptyline in Early Life Stage Zebrafish.

Antidepressants are one of the most globally prescribed classes of pharmaceuticals, and drug target conservation across phyla means that nontarget organisms may be at risk from the effects of exposure. Here, we address the knowledge gap for the effects of chronic exposure (28 days) to the tricyclic antidepressant amitriptyline (AMI) on fish, including for concentrations with environmental relevance, using zebrafish (Danio rerio) as our experimental model. AMI was found to bioconcentrate in zebrafish, was readily transformed to its major active metabolite nortriptyline, and induced a pharmacological effect (downregulation of the gene encoding the serotonin transporter; slc6a4a) at environmentally relevant concentrations (0.03 µg/L and above). Exposures to AMI at higher concentrations accelerated the hatch rate and reduced locomotor activity, the latter of which was abolished after a 14 day period of depuration. The lack of any response on the features of physiology and behavior we measured at concentrations found in the environment would indicate that AMI poses a relatively low level of risk to fish populations. The pseudopersistence and likely presence of multiple drugs acting via the same mechanism of action, however, together with a global trend for increased prescription rates, mean that this risk may be underestimated using current ecotoxicological assessment paradigms.

Nitinol overdose-rescue of acute limb ischemia caused by stenting of the common iliac, external iliac, common femoral, superficial femoral, and popliteal arteries in an actively smoking patient with claudication.

Intermittent claudication (IC) from peripheral arterial disease is typically managed with pharmacologic interventions and lifestyle changes. However, despite societal guidelines, initial endovascular interventions are being used more frequently with an increased incidence of complications, resulting in rapid disease progression to critical and acute limb-threatening ischemia (ALI). The present report describes the case of a patient who developed ALI after treatment of IC at another facility, with malpositioned bilateral common iliac stents, continuous stent extension into the popliteal artery, and acute occlusion of the entirety of the right lower extremity vasculature. This case illustrates how extensive endovascular intervention for IC can result in ALI requiring urgent revascularization.

Are synthetic glucocorticoids in the aquatic environment a risk to fish?

The glucocorticosteroid, or glucocorticoid (GC), system is largely conserved across vertebrates and plays a central role in numerous vital physiological processes including bone development, immunomodulation, and modification of glucose metabolism and the induction of stress-related behaviours. As a result of their wide-ranging actions, synthetic GCs are widely prescribed for numerous human and veterinary therapeutic purposes and consequently have been detected extensively within the aquatic environment. Synthetic GCs designed for humans are pharmacologically active in non-mammalian vertebrates, including fish, however they are generally detected in surface waters at low (ng/L) concentrations. In this review, we assess the potential environmental risk of synthetic GCs to fish by comparing available experimental data and effect levels in fish with those in mammals. We found the majority of compounds were predicted to have insignificant risk to fish, however some compounds were predicted to be of moderate and high risk to fish, although the dataset of compounds used for this analysis was small. Given the common mode of action and high level of inter-species target conservation exhibited amongst the GCs, we also give due consideration to the potential for mixture effects, which may be particularly significant when considering the potential for environmental impact from this class of pharmaceuticals. Finally, we also provide recommendations for further research to more fully understand the potential environmental impact of this relatively understudied group of commonly prescribed human and veterinary drugs.

Intraoperative Vascular Assistance: Essential to an Institution's Ability to Provide Surgical Care.

BACKGROUND: The wide breadth of vascular surgery (VS) training enables vascular surgeons to assist in nonvascular operations and rapidly respond to urgent and emergent needs for intervention. This study aims to evaluate VS secondary operative assistance and intraoperative consultations METHODS: Retrospective review of all operative interventions with a vascular surgeon as secondary surgeon between January 1, 2011 and January 31, 2020 at a single institution. Any cases with VS as primary service were excluded. Patient demographics, operative variables, and in-hospital outcomes were evaluated. RESULTS: Four hundred thirty-seven patients requiring interventions necessitating VS assistance were identified, this included elective, urgent, and emergent operative cases. One hundred thirty-one cases were urgent or emergent and 306 were elective. The median age was 58.0 years (IQR: 40-68.0). Most patients were male (237, 54.2%), White (298, 68.2%), and average BMI was 29.2 +/- 8.5 with ASA ≥4 (143, 32.7%). One hundred seventy (38.9%) cases involved intraoperative consultations, whereas, 267 (61.1%) provided advance notice of need for secondary assistance. The most common services requesting consultations were spine surgery (both orthopedic and neurosurgery) (83, 19%), cardiothoracic surgery (82, 18.8%), and surgical oncology (42, 9.6%). Vascular interventions included revascularization (108, 4.7%), hemorrhage control (94, 21.5%), and exposure (131, 30%). In-hospital mortality was 12.1%. CONCLUSIONS: With the armamentarium of open, endovascular, and hybrid interventions, vascular surgeons are prepared to respond and intervene in nonvascular cases in the event of unexpected vascular compromise, iatrogenic injury, or challenging exposure, as well as assist in planned elective operations. This study reinforces the role of VS in an institution's ability to offer safe and prompt surgical care.

Concomitant Aorto-Caval Reconstruction for Inferior Vena Cava Leiomyosarcoma.

BACKGROUND: Leiomyosarcoma of the inferior vena cava (IVC) is a rare smooth muscle neoplasm typically presenting in the fifth to sixth decades of life with both intraluminal and extraluminal growth patterns. Surgical resection remains the gold standard for nonmetastatic disease and often requires vascular reconstruction. We present an atypical case of leiomyosarcoma involving both the IVC and infrarenal abdominal aorta necessitating reconstruction with intraoperative veno-venous bypass. METHODS: A 63-year-old man initially presenting with back pain was found to have a large mass adjacent to the IVC on MRI, subsequently confirmed to be leiomyosarcoma by biopsy. After 6 months of neoadjuvant chemotherapy, the patient was taken for resection. However, intraoperatively the tumor was found to involve the aorta necessitating combined aorto-caval reconstruction. To facilitate en-bloc resection of the tumor, the aorta was reconstructed first followed by the inferior vena cava using veno-venous bypass. RESULTS: Postoperatively, the patient was taken to the intensive care unit for resuscitation and had an uncomplicated hospital course. He was discharged to rehab 6 days postoperatively and at one year remains free of significant tumor burden with patent aorto-caval bypass grafts. CONCLUSIONS: Primary leiomyosarcoma of the IVC is estimated to have aortic involvement in <10% of cases and concurrent aorto-caval reconstruction can be a well-tolerated option in good surgical candidates. Furthermore, veno-venous bypass can be a useful tool for accomplishing successful oncologic resections. With interdisciplinary collaboration between surgical oncologists, urologists, and vascular surgeons, difficult pathologies can be addressed with good patient outcomes.

Giant visceral artery pseudoaneurysm treated with endovascular transradial coil embolization.

Visceral artery pseudoaneurysms (PSAs) are relatively rare, and cases associated with distal vasculature of the superior mesenteric artery are largely unreported. Visceral artery PSAs, without intervention, can lead to morbidity or mortality from rupture or mesenteric ischemia. Historically, open aneurysmectomy is the gold standard; however, endovascular modalities have emerged as the first-line treatment in patients who are poor surgical candidates and/or have unfavorable anatomy. Herein, we describe a case of a symptomatic PSA of the distal superior mesenteric artery treated via the transradial approach with endovascular coil embolization, showing successful aneurysmal exclusion and preservation of enteric collateral flow.

Form of Supplemental Selenium in Vitamin-Mineral Premixes Differentially Affects Early Luteal and Gestational Concentrations of Progesterone, and Postpartum Concentrations of Prolactin in Beef Cows.

Soils with marginal to deficient levels of selenium (Se) are widespread in the northwest, northeast, and southeast US. Supplementation to the diet of forage-grazing beef cattle with a vitamin-mineral mix containing additional Se is recommended in these geographic regions. We have reported that the form of supplemental Se provided to Angus-cross beef cows can affect circulating levels of progesterone (P4) on day 6 of the estrous cycle, a time when increased P4 is known to promote fertility. The objectives of this study were to (1) confirm and expand upon our initial report that the form of Se provided to cows affects early luteal-phase concentrations of systemic P4, (2) determine the effects of the form of Se on concentrations of P4 during gestation, and (3) determine the effects of the form of Se on concentrations of prolactin (PRL) during lactation. Throughout this study, Angus-cross beef cows had ad libitum access to a vitamin-mineral mix containing 35 ppm of Se in either an inorganic form (ISe) or a 1:1 mix of inorganic and organic forms (MIX). We observed a MIX-induced increase (p = 0.006) in systemic concentrations of P4 on day 7 but not on days 4 or 10 of the estrous cycle, consistent with our earlier report. We observed a MIX-induced increase (p = 0.02) in the systemic concentration of P4 at months 1, 3, 5, and 7 of gestation, and a MIX-induced decrease (p < 0.05) in systemic concentrations of PRL at months 5 and 6 of lactation. In summary, the form of Se provided to cows can be manipulated to affect the early luteal phase and gestational concentrations of P4, and postpartum concentrations of PRL.

Use of the six core surgical indicators from the Lancet Commission on Global Surgery in Colombia: a situational analysis.

BACKGROUND: Surgical, anaesthetic, and obstetric (SAO) health-care system strengthening is needed to address the emergency and essential surgical care that approximately 5 billion individuals lack globally. To our knowledge, a complete, non-modelled national situational analysis based on the Lancet Commission on Global Surgery surgical indicators has not been done. We aimed to undertake a complete situation analysis of SAO system preparedness, service delivery, and financial risk protection using the core surgical indicators proposed by the Commission in Colombia, an upper-middle-income country. METHODS: Data to inform the six core surgical system indicators were abstracted from the Colombian national health information system and the most recent national health survey done in 2007. Geographical access to a Bellwether hospital (defined as a hospital capable of providing essential and emergency surgery) within 2 h was assessed by determining 2 h drive time boundaries around Bellwether facilities and the population within and outside these boundaries. Physical 2 h access to a Bellwether was determined by the presence of a motor vehicle suitable for individual transportation. The Department Administrativo Nacional de Estadística population projection for 2016 and 2018 was used to calculate the SAO provider density. Total operative volume was calculated for 2016 and expressed nationally per 100 000 population. The total number of postoperative deaths that occurred within 30 days of a procedure was divided by the total operative volume to calculate the all-cause, non-risk-adjusted postoperative mortality. The proportion of the population subject to impoverishing costs was calculated by subtracting the baseline number of impoverished individuals from those who fell below the poverty line once out-of-pocket payments were accounted for. Individuals who incurred out-of-pocket payments that were more than 10% of their annual household income were considered to have experienced catastrophic expenditure. Using GIS mapping, SAO system preparedness, service delivery, and cost protection were also contextualised by socioeconomic status. FINDINGS: In 2016, at least 7·1 million people (15·1% of the population) in Colombia did not have geographical access to SAO services within a 2 h driving distance. SAO provider density falls short of the Commission's minimum target of 20 providers per 100 000 population, at an estimated density of 13·7 essential SAO health-care providers per 100 000 population in 2018. Lower socioeconomic status of a municipality, as indicated by proportion of people enrolled in the subsidised insurance regime, was associated with a smaller proportion of the population in the municipality being within 2 h of a Bellwether facility, and the most socioeconomically disadvantaged municipalities often had no SAO providers. Furthermore, Colombian providers appear to be working at or beyond capacity, doing 2690-3090 procedures per 100 000 population annually, but they have maintained a relatively low median postoperative mortality of 0·74% (IQR 0·48-0·84). Finally, out-of-pocket expenses for indirect health-care costs were a key barrier to accessing surgical care, prompting 3·1 million (6·4% of the population) individuals to become impoverished and 9·5 million (19·4% of the population) individuals to incur catastrophic expenditures in 2007. INTERPRETATION: We did a non-modelled, indicator-based situation analysis of the Colombian SAO system, finding that it has not yet met, but is working towards achieving, the targets set by the Lancet Commission on Global Surgery. The observed interdependence of these indicators and correlation with socioeconomic status are consistent with well recognised factors and outcomes of social, health, and health-care inequity. The internal consistency observed in Colombia's situation analysis validates the use of the indicators and has now informed development of an early national SAO plan in Colombia, to set a data-informed stage for implementation and evaluation of timely, safe, and affordable SAO health care, within the National Public Health Decennial Plan, which is due in 2022. FUNDING: Zoll Medical.

Glutathione content and expression of proteins involved with glutathione metabolism differs in longissimus dorsi, subcutaneous adipose, and liver tissues of finished vs. growing beef steers.

Increased tissue redox state may result in sub-optimal growth. Our goal was to determine if glutathione (GSH) content and expression of proteins involved with GSH metabolism change in longissimus dorsi (LD), subcutaneous adipose (SA), and liver tissues of growing vs. finishing steer phenotypes. Tissues were taken from 16 Angus steers (BW = 209 ± 29.4 kg) randomly assigned (n = 8) to develop through Growing (final BW = 301 ± 7.06 kg) vs. Finished (final BW = 576 ± 36.9 kg) growth phases, and at slaughter had achieved different rib-eye area (REA) (53.2, 76.8 cm2), marbling scores (296, 668), and 12th rib adipose thickness (0.54, 1.73 cm), respectively (Amino Acids, doi:10.1007/s00726-018-2540-8). GSH content (mg/g wet tissue) was determined by a commercial assay and the relative content of target protein and mRNA in tissue homogenates was determined by Western blot and reverse-transcribed PCR analyses, respectively. The effect of growth phase (Finished vs. Growing) was assessed by ANOVA using the GLM procedure of SAS. The LD of Finished steers had more (P < 0.04) GSH (42%) and GSH synthesizing (GCLC, 61%; GCLM, 21%) and metabolizing (GPX1, 42%; GPX3, 73%; GGT1, 56%) enzymes, and less (P < 0.02) GPX2 (46%), EAAC1 (30%) and glutamine synthetase (GS) (28%), whereas GTRAP3-18 and ARL6IP1 did not differ (P > 0.57). Principal component analysis found that GSH content of LD was associated with REA and marbling score. The SA of Finished steers had less (P < 0.04) GSH (38%), GSH metabolizing (GPX4, 52%; GGT1, 71%) enzyme mRNA, and GTRAP3-18 (123%) and ARL6IP1 (43%), whereas the mRNA content of GSH-synthesizing enzymes and content of EAAC1 and GS did not differ (P > 0.32). The liver of Finished steers had less (P < 0.02) mRNA content of GSH synthesizing (GCLC, 39%; GSS 29%) and metabolizing (GPX1, 30%) enzymes, and more (P < 0.01) GSTM1 metabolizing enzyme (114%). The change in GSH content as steers fattened indicate an increased antioxidant capacity in the LD of Finished steers, and a decreased antioxidant capacity in SA, consistent with changes in enzyme and transporter expression. Changes in liver enzyme and transporter expression were consistent with no change in GSH content. The relationship of EAAC1 regulatory proteins (GTRAP3-18, ARL6IP1) to GSH, EAAC1, and GS content differs and changes as Growing steers develop into Finished phenotypes. These findings provide mechanistic insight into how antioxidant capacity occurs in tissues of economic and metabolic importance as cattle fatten.

Degradable 3D-Printed Hydrogels Based on Star-Shaped Copolypeptides.

We present a star copolypeptide-based hydrogel ink capable of structural microfabrication using 3D extrusion printing. The material comprises an amphiphilic block copolymer structure of poly(benzyl-l-glutamate)- b-oligo(l-valine), which spontaneously forms hydrogels through hydrophobic interactions. The chemical design allows the bulk phase of the hydrogel to remain intact after application of shear due to its self-recovery behavior. It is demonstrated that the composition of the materials is ideally suited for 3D printing with scaffolds capable of maintaining structural cohesion after extrusion. Post extrusion UV-triggered fixation of the printed structures is carried out, resulting in stable hydrogel constructs. The constructs were found to be degradable, exhibited favorable release of encapsulated molecular cargo, and do not appear to affect the metabolic health of the commonly used fibroblastic cell line Balb/3T3 in the absence of the reactive diluent N, N'-methylenebis(acrylamide). The star copolypeptide inks allow for rapid prototyping enabling the fabrication of defined intricate microstructures, providing a platform for complex scaffold development that would otherwise be unattainable with other processing techniques such as molding or casting.

Forming an academic health department: a case example.

The disconnect between public health practice and its academic base has major implications for training and hiring the future public health workforce, for practice-based research, and ultimately for improving the public's health. To bridge this disconnect, the University of Tennessee Department of Public Health and the Knox County Health Department established an academic health department in early 2011 through a memorandum of understanding. This action followed a long history of informal collaborations, built on mutual trust. The memorandum of understanding identified the scope of academic health department activities, clarified responsibilities of each organization, and created a shared coordinator position. Accomplishments during the first 18 months include improving the efficiency and effectiveness of student field placements; establishing collaborative learning sessions delivered jointly by University of Tennessee Department of Public Health faculty and Knox County Health Department staff; and exploring opportunities for practice-based research. The shared coordinator position and an active steering committee are considered fundamental to achieving sustainable academic-practice linkages.

Iron complex-catalyzed ammonia-borane dehydrogenation. A potential route toward B-N-containing polymer motifs using earth-abundant metal catalysts.

Ammonia-borane (NH(3)BH(3), AB) has garnered interest as a hydrogen storage material due to its high weight percent hydrogen content and ease of H(2) release relative to metal hydrides. As a consequence of dehydrogenation, B-N-containing oligomeric/polymeric materials are formed. The ability to control this process and dictate the identity of the generated polymer opens up the possibility of the targeted synthesis of new materials. While precious metals have been used in this regard, the ability to construct such materials using earth-abundant metals such as Fe presents a more economical approach. Four Fe complexes containing amido and phosphine supporting ligands were synthesized, and their reactivity with AB was examined. Three-coordinate Fe(PCy(3))[N(SiMe(3))(2)](2) (1) and four-coordinate Fe(DEPE)[N(SiMe(3))(2)](2) (2) yield a mixture of (NH(2)BH(2))(n) and (NHBH)(n) products with up to 1.7 equiv of H(2) released per AB but cannot be recycled (DEPE = 1,2-bis(diethylphosphino)ethane). In contrast, Fe supported by a bidentate P-N ligand (4) can be used in a second cycle to afford a similar product mixture. Intriguingly, the symmetric analogue of 4 (Fe(N-N)(P-P), 3), only generates (NH(2)BH(2))(n) and does so in minutes at room temperature. This marked difference in reactivity may be the result of the chemistry of Fe(II) vs Fe(0).

B-N compounds for chemical hydrogen storage.

Hydrogen storage for transportation applications requires high volumetric and gravimetric storage capacity. B-N compounds are well suited as storage materials due to their light weight and propensity for bearing multiple protic (N-H) and hydridic (B-H) hydrogens. This critical review briefly covers the various methods of hydrogen storage, and then concentrates on chemical hydrogen storage using B-N compounds. The simplest B-N compound, ammonia borane (H3NBH3), which has a potential 19.6 wt% hydrogen storage capacity, will be emphasised (127 references).

Linking veterinary and human public-health education: collaborations at the University Of Tennessee.

The increasing demand for veterinarians in public health has created an environment for innovative educational approaches, providing opportunities for veterinary students to gain additional education in public health. At the University of Tennessee, this environment has enabled a collaboration between the College of Veterinary Medicine and the College of Education, Health, and Human Sciences to establish a veterinary concentration in an existing Master of Public Health degree program. The veterinary public-health concentration was approved in 2004. In addition, other courses and initiatives have been developed at the College of Veterinary Medicine, creating stronger collaborations with academic units and public-health professionals.

Liver transplantation for argininosuccinic aciduria: clinical, biochemical, and metabolic outcome.

We report successful liver transplantation in a young adult with argininosuccinic aciduria but without cirrhosis. Plasma amino acid profile normalized and brain magnetic resonance spectroscopy indicated improved metabolism after transplantation. The general well-being of the patient and his quality of life improved. We suggest that orthotopic liver transplantation should be considered for patients with argininosuccinic aciduria even in the absence of cirrhosis, with the aim of correcting (at least in part) central nervous system metabolism, thereby preventing further neurological deterioration.

The Local Public Health System Assessment of MAPP/The National Public Health Performance Standards Local Tool: a community-based, public health practice and academic collaborative approach to implementation.

The Local Public Health System Assessment (LPHSA) in Mobilizing for Action through Planning and Partnerships (MAPP), and the Local Tool of the National Public Health Performance Standards Program (LT/NPHPSP)--which are one in the same-attempt to assess the capacity to provide the essential public health services. Both tools have been utilized in various public health practice settings; however, users have been challenged with the complexity of the tools and time and human resource investment necessary to complete them. The recent Journal of Public Health Management and Practice issue focus on MAPP provided several examples of LPHSA implementation, both as a component of MAPP and as a stand-alone activity in the context of performance standards. The uniqueness in our approach involved a collaborative between a community-based organization, a public health academic program, and a governmental public health agency which conducted the LPHSA in a manner that did not require actual modification of the tool itself, was practical and feasible, and was of benefit and value to all partners.

Ozone and PM2.5 exposure and acute pulmonary health effects: a study of hikers in the Great Smoky Mountains National Park.

To address the lack of research on the pulmonary health effects of ozone and fine particulate matter (

Students in the community: MAPP as a framework for academic-public health practice linkages.

The importance of establishing and sustaining academic-public health practice linkages has been a point of emphasis in the Institute of Medicine reports on public health in 1988 and in 2003. One likely barrier to fostering such linkages is the absence of a clear framework that matches academic requirements to practice realities. This article describes how an academic-public health practice collaborative has used MAPP in a health planning course for Master of Public Health students over a 3-year period, allowing students the opportunity to work in communities with public health practitioners. The specific focus for each of these 3 years has varied, but underlying the work has been a consistent approach to teaching and working in communities with MAPP as the frame of reference. The outcome of this work has been of value to students and faculty, to public health department staff, and, most important, to the communities where this work has taken place. This suggests that there is great potential for using MAPP as a framework for establishing and strengthening academic-public health practice linkages.