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BACKGROUND: Surgical site infections (SSI) following clean and clean-contaminated ambulatory surgery at Bon Secours Cottage Health Services are monitored utilizing a postdischarge surveillance form in addition to traditional surveillance. From January 2000 to December 2002, the clean procedure SSI rate was 0.73% (31/4266) versus 1.58% (15/950) for breast biopsy, P = .04. A case-control study was performed to identify risk factors for infection. METHODS: A case patient was identified as any patient having an ambulatory breast biopsy from January 2000 to December 2002 with SSI identified by the Centers for Disease Control and Prevention (CDC) definition of nosocomial infection. For each case patient, 3 randomly selected control patients were matched by date and procedure. RESULTS: Factors significantly associated with the development of SSI were duration of surgery (case mean, 71.7 minutes vs control mean, 34.7 minutes, P < .01) and presence of surgical drains (26.7% of cases vs 6.7% of controls, P = .04). Factors determined not to be associated with SSI were obesity (P = .88) and preoperative needle localization (P = .88). CONCLUSIONS: We conclude that there is a significant difference between the breast biopsy infection rate and the clean procedure infection rate in ambulatory surgery. Duration of surgery and presence of surgical drains were associated with increased infection rate. [ABSTRACT FROM AUTHOR]

Background:  In this study, we explored the relationship between adverse childhood experiences and childhood protective factors (i.e., resilience) with outpatient treatment outcomes among youths receiving buprenorphine-based medication for opioid use disorder over a six-month period. Methods:  An observational study was conducted among 42 participants utilizing the modified Adverse Childhood Experience Questionnaire and the Southern Kennebec Healthy Start Resilience survey. Treatment outcomes included the end of treatment, buprenorphine-based medication treatment nonadherence, and opioid relapse. Cox proportional hazard models were fit for all treatment outcomes. Results:  Reported adverse childhood experiences were high compared with the national average and demonstrated a significant inverse association with time to buprenorphine treatment nonadherence. Total resilience score was not significantly associated with any treatment outcome. Analysis of potential confounders and other covariates likewise demonstrated no relationship. Conclusions:  Higher reported adverse childhood experience scores were associated with greater hazard of buprenorphine-based medication nonadherence. This finding underscores the need for ACE screening and trauma-informed care in this population.

Cholesterol is a key sterol whose homeostasis is primarily maintained through bile acid metabolism. Proper bile acid formation is vital for nutrient and fat-soluble vitamin absorption and emulsification of lipids. Synthesis of bile acids occurs through two main pathways, both of which rely on 3β-hydroxy-Δ 5 -C 27 -steroid oxidoreductase (HSD3B7) to begin epimerization of the 3β hydroxyl of cholesterol into its active 3α conformation. In this sequence, HSD3B7 catalyzes the dehydrogenation of the 3β-hydroxy group followed by isomerization of the Δ 5 -cholestene-3-one. These reactions are some of the many steps that transform cholesterol for either storage or secretion. HSD3B7 has distinct activity from other 3β-HSD family members leaving significant gaps in our understanding of its mode of catalysis and substrate specificity. In addition, the role of HSD3B7 in health and disease positions it as a metabolic vulnerability that could be harnessed as a therapeutic target. To this end, we evaluated the mechanism of HSD3B7 catalysis and reveal that HSD3B7 displays activity toward diverse 7α-hydroxylated oxysterols. HSD3B7 retains its catalytic efficiency toward these substrates, suggesting that its substrate binding pocket can withstand changes in polarity upon alterations to this hydrocarbon tail. Experiments aimed at determining substrate order are consistent with HSD3B7 catalyzing a sequential ordered bi-bi reaction mechanism with the binding of NAD + followed by 7α-hydroxycholesterol to form a central complex. HSD3B7 bifunctional activity is dependent on membrane localization through a putative membrane-associated helix giving insight into potential regulation of enzyme activity. We found strong binding of the NADH product thought to activate the isomerization reaction. Homology models of HSD3B7 reveal a potential substrate pocket that allows for oxysterol binding, and mutagenesis was utilized to support this model. Together, these studies offer an understanding of substrate specificity and kinetic mechanism of HSD3B7, which can be exploited for future drug development., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article except for T.M.P. who is the cofounder of Penzymes and is a consultant for Sage Therapeutics and Propella, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In physiology education, students must learn to recognize and construct causal explanations. This challenges students, in part, because causal explanations in biology manifest in different varieties. Unlike other natural sciences, causal mechanisms in physiology support physiological functions and reflect biological adaptations. Therefore, students must distinguish between questions that prompt a proximate or an ultimate explanation. In the present investigation, we aimed to determine how these different varieties of student knowledge coordinate within students' written explanations. Prior research in science education demonstrates that students present specific challenges when distinguishing between proximate and ultimate explanations: students appear to conflate the two or construct other nonmechanistic explanations. This investigation, however, demonstrates that analytic frameworks can distinguish between students' proximate and ultimate explanations when they are provided explanatory scaffolds that contextualize questions. Moreover, these scaffolds and prompts help students distinguish between physiological functions and the cellular and molecular mechanisms that underpin them. Together, these findings deliver insight into the context-sensitive nature of student knowledge in physiology education and offer an analytic framework for identifying and characterizing student knowledge in physiology. NEW & NOTEWORTHY Why ask why? How questions posed in physiology task students with developing their mechanistic reasoning. Why questions sometimes undermine this reasoning. Prior research, however, also illustrates that framing the context of a question explicitly supports students in distinguishing between question types. We further illustrate how providing such context in the form of explanatory scaffolds and prompts allows students to tap different and useful varieties of knowledge when constructing written explanations.

Clear cell renal cell carcinoma (ccRCC) incidence has risen steadily over the last decade. Elevated lipid uptake and storage is required for ccRCC cell viability. As stored cholesterol is the most abundant component in ccRCC intracellular lipid droplets, it may also play an important role in ccRCC cellular homeostasis. In support of this hypothesis, ccRCC cells acquire exogenous cholesterol through the high-density lipoprotein receptor SCARB1, inhibition or suppression of which induces apoptosis. Here, we showed that elevated expression of 3 beta-hydroxy steroid dehydrogenase type 7 (HSD3B7), which metabolizes cholesterol-derived oxysterols in the bile acid biosynthetic pathway, is also essential for ccRCC cell survival. Development of an HSD3B7 enzymatic assay and screening for small-molecule inhibitors uncovered the compound celastrol as a potent HSD3B7 inhibitor with low micromolar activity. Repressing HSD3B7 expression genetically or treating ccRCC cells with celastrol resulted in toxic oxysterol accumulation, impaired proliferation, and increased apoptosis in vitro and in vivo. These data demonstrate that bile acid synthesis regulates cholesterol homeostasis in ccRCC and identifies HSD3B7 as a plausible therapeutic target., Significance: The bile acid biosynthetic enzyme HSD3B7 is essential for ccRCC cell survival and can be targeted to induce accumulation of cholesterol-derived oxysterols and apoptotic cell death., (©2024 American Association for Cancer Research.)

Graphs are ubiquitous tools in science that allow one to explore data patterns, design studies, communicate findings, and make claims. This essay is a companion to the online, evidence-based interactive guide intended to help inform instructors' decision-making in how to teach graph reading, interpretation, construction, and evaluation within the discipline of biology. We provide a framework with a focus on six instructional practices that instructors can utilize when designing graphing activities: use data to engage students, teach graphing grounded in the discipline, practice explicit instruction, use real world "messy" data, utilize collaborative work, and emphasize reflection. Each component of this guide is supported by summaries of and links to articles that can inform graphing practices. The guide also contains an instructor checklist that summarizes key points with actionable steps that can guide instructors as they work towards refining and incorporating graphing into their classroom practice and emerging questions in which further empirical studies are warranted.

Background: The nationwide shortage of mental health resources often disproportionately affects rural areas. As innovative strategies are required to address mental health resource shortages in rural areas, telepsychiatry consultation (TPC) may represent a population health-oriented approach to bridge this gap. In this case report, we examine the use of TPC from an academic consultation-liaison psychiatry service to a rural community hospital. Case Report: We describe the case of a woman with Wernicke encephalopathy seeking to leave the hospital against medical advice and the role that the TPC service played in the patient's evaluation and management, including assessing decision-making capacity. Discussion: We then examine benefits and limitations of the service, including a narrative review of the relevant, but limited, available literature as well as suggestions for how the service may be improved and incorporated into psychiatry residency and fellowship training in the future.

Explaining biological phenomena requires understanding how different processes function and describing interactions between components at various levels of organization over time and space in biological systems. This is a desired competency yet is a complicated and often challenging task for undergraduate biology students. Therefore, we need a better understanding of their integrated knowledge regarding important biological concepts. Informed by the theory of knowledge integration and mechanistic reasoning, in this qualitative case study, we elicited and characterized knowledge networks of nine undergraduate biology students. We investigated students' conceptions of and the various ways they connect three fundamental subsystems in biology: 1) gene regulation, 2) cell-cell communication, and 3) phenotypic expression. We found that only half of the conceptual questions regarding the three subsystems were answered correctly by the majority of students. Knowledge networks tended to be linear and unidirectional, with little variation in the types of relationships displayed. Students did not spontaneously express mechanistic connections, mainly described undefined, cellular, and macromolecular levels of organization, and mainly discussed unspecified and intracellular localizations. These results emphasize the need to support students' understanding of fundamental concepts, and promoting knowledge integration in the classroom could assist students' ability to understand biological systems.

Substance use disorders and feeding and eating disorders (FEDs) often manifest in early adolescence, are difficult to treat, and tend to co-occur. Despite their co-occurrence, little is known about their shared risk factors. A cross-sectional study was conducted to compare standardized measures of adverse childhood experiences (ACEs) and protective factors among 90 adolescents and young adults seeking outpatient treatment for either opioid use disorder (OUD) or an FED. These were assessed using the Modified Adverse Childhood Experience Survey and Southern Kennebec Healthy Start Resilience Survey. Reported ACEs were high in both groups compared with the national average, and those with OUD were more likely to endorse ≥4 resilience factors. Meanwhile, the prevalence of emotional neglect, household mental illness, and peer victimization/isolation/rejection was similar between groups. Opioid use disorder patients were also less likely to endorse ≥9 resilience factors. Health providers should be mindful to assess for trauma and resiliency in both these populations.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry., Prim Care Companion CNS Disord 2023;25(4):22f03471 ., Author affiliations are listed at the end of this article., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

N-terminal acetylation is a chemical modification carried out by N-terminal acetyltransferases. A major member of this enzyme family, NatB, acts on much of the human proteome, including α-synuclein (αS), a synaptic protein that mediates vesicle trafficking. NatB acetylation of αS modulates its lipid vesicle binding properties and amyloid fibril formation, which underlies its role in the pathogenesis of Parkinson's disease. Although the molecular details of the interaction between human NatB (hNatB) and the N-terminus of αS have been resolved, whether the remainder of the protein plays a role in interacting with the enzyme is unknown. Here, we execute the first synthesis, by native chemical ligation, of a bisubstrate inhibitor of NatB consisting of coenzyme A and full-length human αS, additionally incorporating two fluorescent probes for studies of conformational dynamics. We use cryo-electron microscopy (cryo-EM) to characterize the structural features of the hNatB/inhibitor complex and show that, beyond the first few residues, αS remains disordered when in complex with hNatB. We further probe changes in the αS conformation by single molecule Förster resonance energy transfer (smFRET) to reveal that the C-terminus expands when bound to hNatB. Computational models based on the cryo-EM and smFRET data help to explain the conformational changes as well as their implications for hNatB substrate recognition and specific inhibition of the interaction with αS. Beyond the study of αS and NatB, these experiments illustrate valuable strategies for the study of challenging structural biology targets through a combination of protein semi-synthesis, cryo-EM, smFRET, and computational modeling.

Understanding molecular processes and coordinating the various activities across levels of organization in biological systems is a complicated task, yet many curricular guidelines indicate that undergraduate students should master it. Employing mechanistic reasoning can facilitate describing and investigating biological phenomena. Biofilms are an important system in microbiology and biology education. However, few empirical studies have been conducted on student learning of biofilms or how students utilize mechanistic reasoning related to systems thinking to explain biofilm formation. Using mechanistic reasoning and the theory of knowledge integration as conceptual and analytical frameworks, we examined the features of 9 undergraduate biology students' mechanistic models of a specific transition point in biofilm development. From these data, we constructed a model of knowledge integration in the context of biofilms, which categorizes students' knowledge based on features of their descriptions (e.g., entities, correct connections, and the nature of connections). We found that 4 of 9 students produced a fragmented model, 4 of 9 students produced a transitional model, and 1 student produced a connected model. Overall, students often did not discuss cell-cell communication mechanics in their mechanistic models and rarely included the role of gene regulation. Most connections were considered nonnormative and lacked important entities, leading to an abundance of unspecified causal connections. We recommend increasing instructional support of mechanistic reasoning within systems (e.g., identifying entities across levels of organization and their relevant activities) and creating opportunities for students to grapple with their understanding of various biological concepts and to explore how processes interact and connect in a complex system., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Flowers et al.)

Science educators report that students struggle with understanding, using, and evaluating the evidence underpinning scientific knowledge. However, there are not many studies focused on helping instructors address those difficulties. Here, we report on a laboratory instructor's scaffolding of students' evidentiary reasoning with and about evidence for evolutionary trees with guidance from the Conceptual Analysis of Disciplinary Evidence (CADE) framework, which links biological knowledge with epistemic considerations. To consider both domain-general and discipline-specific aspects of evidence, CADE was implemented to inform scaffolds in two ways: (1) generic evidence scaffolds (GES) reminded students of general epistemic considerations; (2) disciplinary evidence scaffolds (DES) explicitly reminded students of the disciplinary knowledge of relevance for considering biological evidence. An instructor's lab discussions were compared before and after they had a workshop with CADE. CADE helped the lab instructor facilitate students' evidentiary reasoning about evolutionary trees. In comparison to baseline, both GES and DES discussions covered more aspects and relationships among types of evidence for evolutionary tree-thinking and the instructor prompted more kinds of general epistemic considerations and biological knowledge. DES discussions emphasized the importance of disciplinary knowledge for research design. The CADE framework guided planning and implementation of intentional scaffolding aimed at guiding evidentiary reasoning., Supplementary Information: The online version contains supplementary material available at 10.1007/s11191-023-00435-6., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

N-terminal acetylation occurs on over 80% of human proteins and is catalyzed by a family of N-terminal acetyltransferases (NATs). All NATs contain a small catalytic subunit, while some also contain a large auxiliary subunit that facilitates catalysis and ribosome targeting for co-translational acetylation. NatC is one of the major NATs containing an NAA30 catalytic subunit, but uniquely contains two auxiliary subunits, large NAA35 and small NAA38. Here, we report the cryo-EM structures of human NatC (hNatC) complexes with and without NAA38, together with biochemical studies, to reveal that NAA38 increases the thermostability and broadens the substrate-specificity profile of NatC by ordering an N-terminal segment of NAA35 and reorienting an NAA30 N-terminal peptide binding loop for optimal catalysis, respectively. We also note important differences in engagement with a stabilizing inositol hexaphosphate molecule between human and yeast NatC. These studies provide new insights for the function and evolution of the NatC complex., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Protein N-terminal acetyltransferase D (NatD, NAA40) that specifically acetylates the alpha-N-terminus of histone H4 and H2A has been implicated in various diseases, but no inhibitor has been reported for this important enzyme. Based on the acetyl transfer mechanism of NatD, we designed and prepared a series of highly potent NatD bisubstrate inhibitors by covalently linking coenzyme A to different peptide substrates via an acetyl or propionyl spacer. The most potent bisubstrate inhibitor displayed an apparent K i value of 1.0 nM. Biochemical studies indicated that bisubstrate inhibitors are competitive to the peptide substrate and noncompetitive to the cofactor, suggesting that NatD undergoes an ordered Bi-Bi mechanism. We also demonstrated that these inhibitors are highly specific toward NatD, displaying about 1000-fold selectivity over other closely related acetyltransferases. High-resolution crystal structures of NatD bound to two of these inhibitors revealed the molecular basis for their selectivity and inhibition mechanism, providing a rational path for future inhibitor development.

The sesquiterpene cyclase epi -isozizaene synthase (EIZS) catalyzes the cyclization of farnesyl diphosphate to form the tricyclic precursor of the antibiotic albaflavenone. The hydrophobic active site is largely defined by aromatic residues that direct a multistep reaction sequence through multiple carbocation intermediates. The previous substitution of polar residues for a key aromatic residue, F96, converts EIZS into a high-fidelity sesquisabinene synthase: the F96S, F96M, and F96Q variants generate 78%, 91%, and 97% sesquisabinene A, respectively. Here, we report high-resolution X-ray crystal structures of two of these reprogrammed cyclases. The structures of the F96M EIZS-Mg 2+ 3 -risedronate and F96M EIZS-Mg 2+ 3 -inorganic pyrophosphate-benzyltriethylammonium cation complexes reveal structural changes in the F96 aromatic cluster that redirect the cyclization pathway leading from the bisabolyl carbocation intermediate in catalysis. The structure of the F96S EIZS-Mg 2+ 3 -neridronate complex reveals a partially occupied inhibitor and an enzyme active site caught in transition between open and closed states. Finally, three structures of wild-type EIZS complexed with the bisphosphonate inhibitors neridronate, pamidronate, and risedronate provide a foundation for understanding binding differences between wild-type and variant enzymes. These structures provide new insight regarding active site flexibility, particularly with regard to the potential for subtle expansion and contraction to accommodate ligands of varying sizes as well as bound water molecules. Additionally, these structures highlight the importance of conformational changes in the F96 aromatic cluster that could influence cation-π interactions with carbocation intermediates in catalysis.

Introduction: Contradictory social policies and attitudes about gender diversity raise questions about how we should understand the current status of the historical 'heterosexual' gender regime., Conclusion: Drawing on the work of the feminist philosopher and psychoanalyst Luce Irigaray, this essay argues that sexual difference is the irreducible starting point for all meaning, sense, morality and affect.

When a student explains a biological phenomenon, does the answer reflect only the product of retrieving knowledge or does it also reflect a dynamic process of constructing knowledge ? To gain insight into students' dynamic knowledge, we leveraged three analytic frameworks-structures-behaviors-functions (SBF), mental models (MM), and conceptual dynamics (CD). To assess the stability of student knowledge, we asked undergraduate students to explain the same physiological phenomenon three times-once verbally, once after drawing, and once after interpreting a diagram. The SBF analysis illustrated fine-grained dynamic knowledge between tasks. The MM analysis suggested global stability between tasks. The CD analysis demonstrated local instability within tasks. The first two analyses call attention to differences between students' knowledge about the parts of systems and their organization. The CD analysis, however, calls attention to similar learning mechanisms that operate differently vis-à-vis external representations. Students with different mental models deliberated localization or where to locate the structures and mechanisms that mediate physiological responses, but students made these deliberations during different tasks and arrived at different conclusions. These results demonstrate the utility of incorporating dynamic approaches to complement other analytic approaches and motivate future research agendas in biology education research.

Background : The use of the natural product, kratom, has increased significantly in recent years. The active compounds in kratom have been shown to produce both opioid and stimulant-like effects. While kratom is marketed as a safe, non-addictive method to treat pain and opioid withdrawal, there have been reports demonstrating that kratom is physiologically addictive and linked to overdose deaths. A limited number of case-reports are available describing treatment of kratom use disorder in middle-aged adults, generally in the context of chronic pain and in inpatient settings. Our case is unique in that we describe outpatient treatment of kratom use disorder in a young adult with comorbid attention deficit hyperactivity disorder (ADHD) and in the absence of chronic pain. Case : A 20-year-old college student with ADHD presented to an office-based opioid agonist treatment clinic (OBOT) for treatment of kratom use disorder. He was unable to attend inpatient or residential substance use treatment due to work and school obligations. Additionally, he had stopped taking his prescribed stimulant due to cardiac side effects. The OBOT team successfully initiated buprenorphine-naloxone (BUP/NAL) sublingual films via home induction to treat his kratom use disorder. The patient is being monitored monthly with plans to slowly taper his BUP/NAL dose as tolerated. Discussion : We present a case of a young adult male with kratom use disorder, complicated by a diagnosis of ADHD, successfully treated with BUP/NAL via home induction. The patient is currently kratom-free, reports improved mood and sleep patterns since initiating BUP/NAL, and is able to once again tolerate his ADHD stimulant medication. Healthcare providers should be aware of the use of kratom and consider utilizing BUP/NAL to treat dependence to this botanical drug.

tRNA H is guanylyltransferase (Thg1) specifies eukaryotic tRNA H is identity by catalysing a 3'-5' non-Watson-Crick (WC) addition of guanosine to the 5'-end of tRNA H is . Thg1 family enzymes in Archaea and Bacteria, called Thg1-like proteins (TLPs), catalyse a similar but distinct 3'-5' addition in an exclusively WC-dependent manner. Here, a genetic system in Saccharomyces cerevisiae was employed to further assess the biochemical differences between Thg1 and TLPs. Utilizing a novel 5'-end sequencing pipeline, we find that a Bacillus thuringiensis TLP sustains the growth of a thg1Δ strain by maintaining a WC-dependent addition of U -1 across from A 73 . Additionally, we observe 5'-end heterogeneity in S. cerevisiae small nucleolar RNAs (snoRNAs), an observation that may inform methods of annotation and mechanisms of snoRNA processing., (© 2019 Federation of European Biochemical Societies.)

As undergraduate biology curricula increasingly aim to provide students with access to courses and experiences that engage them in the practices of science, tools are needed for instruction, evaluation, and research around student learning. One of the important skills for undergraduate biology students to master is the selection and creation of appropriate graphs to summarize data they acquire through investigations in their course work and research experiences. Graphing is a complex skill, and there are few, discipline-informed tools available for instructors, students, and researchers to use. Here, we describe the development of a graph rubric informed by literature from the learning sciences, statistics, representations literature, and feedback and use of the rubric by a variety of users. The result is an evidence-based, analytic rubric that consists of categories essential for graph choice and construction: graph mechanics, graph communication, and graph choice. Each category of the rubric can be evaluated at three levels of achievement. Our analysis demonstrates the potential for the rubric to provide formative feedback to students and allow instructors to gauge and guide learning and instruction. We further discuss and identify potentially interesting research targets for science education researchers.

Since 2009, the U.S. National Science Foundation Directorate for Biological Sciences has funded Research Coordination Networks (RCN) aimed at collaborative efforts to improve participation, learning, and assessment in undergraduate biology education (UBE). RCN-UBE projects focus on coordination and communication among scientists and educators who are fostering improved and innovative approaches to biology education. When faculty members collaborate with the overarching goal of advancing undergraduate biology education, there is a need to optimize collaboration between participants in order to deeply integrate the knowledge across disciplinary boundaries. In this essay we propose a novel guiding framework for bringing colleagues together to advance knowledge and its integration across disciplines, the "Five 'C's' of Collaboration: Commitment, Collegiality, Communication, Consensus, and Continuity." This guiding framework for professional network practice is informed by both relevant literature and empirical evidence from community-building experience within the RCN-UBE Advancing Competencies in Experimentation-Biology (ACE-Bio) Network. The framework is presented with practical examples to illustrate how it might be used to enhance collaboration between new and existing participants in the ACE-Bio Network as well as within other interdisciplinary networks.

Undergraduate biology education reform aims to engage students in scientific practices such as experimental design, experimentation, and data analysis and communication. Graphs are ubiquitous in the biological sciences, and creating effective graphical representations involves quantitative and disciplinary concepts and skills. Past studies document student difficulties with graphing within the contexts of classroom or national assessments without evaluating student reasoning. Operating under the metarepresentational competence framework, we conducted think-aloud interviews to reveal differences in reasoning and graph quality between undergraduate biology students, graduate students, and professors in a pen-and-paper graphing task. All professors planned and thought about data before graph construction. When reflecting on their graphs, professors and graduate students focused on the function of graphs and experimental design, while most undergraduate students relied on intuition and data provided in the task. Most undergraduate students meticulously plotted all data with scaled axes, while professors and some graduate students transformed the data, aligned the graph with the research question, and reflected on statistics and sample size. Differences in reasoning and approaches taken in graph choice and construction corroborate and extend previous findings and provide rich targets for undergraduate and graduate instruction., (© 2017 A. Angra and S. M. Gardner. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Physiology demands systems thinking: reasoning within and between levels of biological organization and across different organ systems. Many physiological mechanisms explain how structures and their properties interact at one level of organization to produce emergent functions at a higher level of organization. Current physiology principles, such as structure-function relations, selectively neglect mechanisms by not mentioning this term explicitly. We explored how students characterized mechanisms and functions to shed light on how students make sense of these terms. Students characterized mechanisms as 1 ) processes that occur at levels of organization lower than that of functions; and 2 ) as detailed events with many steps involved. We also found that students produced more variability in how they characterized functions compared with mechanisms: students characterized functions in relation to multiple levels of organization and multiple definitions. We interpret these results as evidence that students see mechanisms as holding a more narrow definition than used in the biological sciences, and that students struggle to coordinate and distinguish mechanisms from functions due to cognitive processes germane to learning in many domains. We offer the instructional suggestion that we scaffold student learning by affording students opportunities to relate and also distinguish between these terms so central to understanding physiology., (Copyright © 2017 the American Physiological Society.)

Recent recommendations for biology education highlight the role of authentic research experiences early in undergraduate education as a means of increasing the number and quality of biology majors. These experiences will inform students on the nature of science, increase their confidence in doing science, as well as foster critical thinking skills, an area that has been lacking despite it being one of the desired outcomes at undergraduate institutions and with future employers. With these things in mind, we have developed an introductory biology laboratory course where students design and execute an authentic microbiology research project. Students in this course are assimilated into the community of researchers by engaging in scholarly activities such as participating in inquiry, reading scientific literature, and communicating findings in written and oral formats. After three iterations of a semester-long laboratory course, we found that students who took the course showed a significant increase in their understanding of the nature of authentic research and their level of critical thinking skills.

The inferior colliculus (IC) receives ascending excitatory and inhibitory inputs from multiple sources, but how these auditory inputs converge to generate IC spike patterns is poorly understood. Simulating patterns of in vivo spike train data from cellular and synaptic models creates a powerful framework to identify factors that contribute to changes in IC responses, such as those resulting in age-related loss of temporal processing. A conductance-based single neuron IC model was constructed, and its responses were compared to those observed during in vivo IC recordings in rats. IC spike patterns were evoked using amplitude-modulated tone or noise carriers at 20-40 dB above threshold and were classified as low-pass, band-pass, band-reject, all-pass, or complex based on their rate modulation transfer function tuning shape. Their temporal modulation transfer functions were also measured. These spike patterns provided experimental measures of rate, vector strength, and firing pattern for comparison with model outputs. Patterns of excitatory and inhibitory synaptic convergence to IC neurons were based on anatomical studies and generalized input tuning for modulation frequency. Responses of modeled ascending inputs were derived from experimental data from previous studies. Adapting and sustained IC intrinsic models were created, with adaptation created via calcium-activated potassium currents. Short-term synaptic plasticity was incorporated into the model in the form of synaptic depression, which was shown to have a substantial effect on the magnitude and time course of the IC response. The most commonly observed IC response sub-types were recreated and enabled dissociation of inherited response properties from those that were generated in IC. Furthermore, the model was used to make predictions about the consequences of reduction in inhibition for age-related loss of temporal processing due to a reduction in GABA seen anatomically with age.

In Enterobacteriaceae, the ProP protein, which takes up proline and glycine betaine, is subject to a post-translational control mechanism that increases its activity at high osmolarity. In order to investigate the osmoregulatory mechanism of the Salmonella enterica ProP, we devised a positive selection for mutations that conferred increased activity on this protein at low osmolarity. The selection involved the isolation of mutations in a proline auxotroph that resulted in increased accumulation of proline via the ProP system in the presence of glycine betaine, which is a competitive inhibitor of proline uptake by this permease. This selection was performed by first-year undergraduates in two semesters of a research-based laboratory course. The students generated sixteen mutations resulting in six different single amino acids substitutions. They determined the effects of the mutations on the growth rates of the cells in media of high and low osmolarity in the presence of low concentrations of proline or glycine betaine. Furthermore, they identified the mutations by DNA sequencing and displayed the mutated amino acids on a putative three-dimensional structure of the protein. This analysis suggested that all six amino acid substitutions are residues in trans-membrane helices that have been proposed to contribute to the formation of the transport pore, and, thus, may affect the substrate binding site of the protein.

Inquiry-based laboratory instruction has been shown to actively engage students in the content and skills being taught. These courses are further intended to teach students not only what is known, but also the process by which investigators come to know it. We sought to take this approach one step further and incorporate novel research questions into an inquiry-based laboratory model early in the undergraduate course of study. In this research-based introductory laboratory course, first-year students acquired basic lab skills not just for their own sake, but rather within the context of a research question of a member of the faculty. Student projects investigated potential neuroanatomical changes in animal models of dyslexia and aging and included measurements of neuron numbers and levels and distribution of neuronal proteins. Students played an active role in designing and implementing an experimental plan, explored data analysis techniques, and reflected on the results that they obtained in scholarly forms such as research papers and a departmental poster session. Student feedback on this approach has been extremely positive, and the data collected were research quality preliminary data that are being actively pursued for further study. Based on our encouraging experiences, we conclude that designing an introductory course around novel research, including some assessments modeled after scholarly practices, provides motivation and excitement for the students, instills good scientific habits, and can potentially benefit departmental research.

Nonhuman primates have been a common animal model to evaluate experimentally induced malformations. Reports on spontaneous malformations are important in determining the background incidence of congenital anomalies in specific species and in evaluating experimental results. Here we report on a stillborn cynomolgus monkey (Macaca fascicularis) with multiple congenital anomalies from the colony maintained at the Southwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, Texas. Physical findings included low birth weight, craniorachischisis, facial abnormalities, omphalocele, malrotation of the gut with areas of atresia and intussusception, a Meckel diverticulum, arthrogryposis, patent ductus arteriosus, and patent foramen ovale. The macaque had normal male external genitalia, but undescended testes. Gestational age was unknown but was estimated from measurements of the limbs and other developmental criteria. Although cytogenetic analysis was not possible due to the tissues being in an advanced state of decomposition, array Comparative Genomic Hybridization analysis using human bacterial artificial chromosome clones was successful in effectively eliminating aneuploidy or any copy number changes greater than approximately 3-5 Mb as a cause of the malformations. Further evaluation of the animal included extensive imaging of the skeletal and neural tissue defects. The animal's congenital anomalies are discussed in relation to the current hypotheses attempting to explain the frequent association of neural tube defects with other abnormalities., (Copyright © 2011 Wiley-Liss, Inc.)

We have reported differential short- and long-term dysregulation of the neuroendocrine stress response after traumatic brain injury (TBI) produced by controlled cortical impact (CCI). We have now investigated three possible mechanisms for this TBI-induced dysregulation: (1) effects on the sensitivity of negative-feedback systems to glucocorticoids; (2) effects on the sensitivity of pituitary corticotrophs to corticotropin-releasing hormone (CRH); and (3) effects on neuronal loss in the hilar region of the dentate gyrus and in the CA3b layer of the dorsal hippocampus. TBI was induced to the left parietal cortex in adult male rats with a pneumatic piston, at two different impact velocities and compression depths, to produce either moderate or mild CCI. At 7 and 35 days after surgery, the rats were injected SC with the synthetic glucocorticoid analog dexamethasone (DEX; 0.01, 0.10, or 1.00 mg/kg) or saline, and 2 h later were subjected to 30 min of restraint stress and tail vein blood collection. Whereas all doses of DEX suppressed corticosterone (CORT) and adrenocorticotropic hormone (ACTH) responses to stress on both days, CORT and ACTH were significantly more suppressed after 0.01 mg/kg DEX in the moderate TBI group than in the mild TBI or sham groups. At both 7 and 35 days post-TBI, CRH (1.0 and 10.0 microg/kg IP) stimulated CORT and ACTH in all rats, regardless of injury condition. Hippocampal cell loss was greatest at 48 days after moderate TBI. Enhanced sensitivity to glucocorticoid negative feedback and greater hippocampal cell loss, but not altered pituitary responses to CRH, contribute to the short- and long-term attenuation of the neuroendocrine stress response following moderate TBI. The role of TBI-induced alterations in glucocorticoid receptors in limbic system sites in enhanced glucocorticoid feedback sensitivity requires further investigation.

A recently described form of synaptic plasticity results in dynamic changes in the calcium permeability of synaptic AMPA receptors. Since the AMPA receptor GluR2 subunit confers calcium permeability, this plasticity is thought to occur through the dynamic exchange of synaptic GluR2-lacking and GluR2-containing receptors. To investigate the molecular mechanisms underlying this calcium-permeable AMPA receptor plasticity (CARP), we examined whether AMPA receptor exchange was mediated by subunit-specific protein-protein interactions. We found that two GluR2-interacting proteins, the PDZ domain-containing Protein interacting with C kinase (PICK1) and N-ethylmaleimide sensitive fusion protein (NSF), are specifically required for CARP. Furthermore, PICK1, but not NSF, regulates the formation of extrasynaptic plasma membrane pools of GluR2-containing receptors that may be laterally mobilized into synapses during CARP. These results demonstrate that PICK1 and NSF dynamically regulate the synaptic delivery of GluR2-containing receptors during CARP and thus regulate the calcium permeability of AMPA receptors at excitatory synapses.

The composition of AMPA receptors in patches excised from somata and dendrites of six cell types in the mammalian cochlear nuclei was probed and compared electrophysiologically and pharmacologically with the rapid application of glutamate. Cells excited predominantly by auditory nerve fibers had AMPA receptors with exceptionally rapid gating (submillisecond deactivation and desensitization time constants). The nonlinear current-voltage relationship in the presence of spermine showed that few of these receptors had GluR2 subunits, and the insensitivity of desensitization to cyclothiazide indicated that they contained mostly flop splice variants. At synapses made by parallel fibers, AMPA receptors were slowly gating (time constants of deactivation and desensitization >1 msec) and contained higher levels of GluR2 and flip isoforms. However, receptors at auditory nerve synapses on cells that also receive parallel fiber input, the fusiform cells, had intermediate properties with respect to kinetics and contained GluR2 and flip isoforms. Given the diverse biophysical properties, patterns of innervation, patterns of electrical activity, and targets of each cell type in vivo, these data indicate that the kinetics and permeation properties of AMPA receptors are linked to factors associated with synaptic connectivity.

The anatomical and biophysical specializations of octopus cells allow them to detect the coincident firing of groups of auditory nerve fibers and to convey the precise timing of that coincidence to their targets. Octopus cells occupy a sharply defined region of the most caudal and dorsal part of the mammalian ventral cochlear nucleus. The dendrites of octopus cells cross the bundle of auditory nerve fibers just proximal to where the fibers leave the ventral and enter the dorsal cochlear nucleus, each octopus cell spanning about one-third of the tonotopic array. Octopus cells are excited by auditory nerve fibers through the activation of rapid, calcium-permeable, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors. Synaptic responses are shaped by the unusual biophysical characteristics of octopus cells. Octopus cells have very low input resistances (about 7 M Omega), and short time constants (about 200 microsec) as a consequence of the activation at rest of a hyperpolarization-activated mixed-cation conductance and a low-threshold, depolarization-activated potassium conductance. The low input resistance causes rapid synaptic currents to generate rapid and small synaptic potentials. Summation of small synaptic potentials from many fibers is required to bring an octopus cell to threshold. Not only does the low input resistance make individual excitatory postsynaptic potentials brief so that they must be generated within 1 msec to sum but also the voltage-sensitive conductances of octopus cells prevent firing if the activation of auditory nerve inputs is not sufficiently synchronous and depolarization is not sufficiently rapid. In vivo in cats, octopus cells can fire rapidly and respond with exceptionally well-timed action potentials to periodic, broadband sounds such as clicks. Thus both the anatomical specializations and the biophysical specializations make octopus cells detectors of the coincident firing of their auditory nerve fiber inputs.

AMPA receptors mediate rapid glutamatergic synaptic transmission. In the mammalian cochlear nuclei, neurons receive excitatory input from either auditory nerve fibers, parallel fibers, or both fiber systems. The functional correlates of differences in the source of input were examined by recording AMPA receptor-mediated, miniature EPSCs (mEPSCs) in whole-cell voltage-clamp mode from identified neurons. Bushy, octopus, and T-stellate cells of the ventral cochlear nucleus (VCN) and tuberculoventral cells of the dorsal cochlear nucleus (DCN) receive most of their excitatory input from the auditory nerve; fusiform cells receive excitatory inputs from both the auditory nerve and parallel fibers; cartwheel cells receive excitatory input from parallel fibers alone. mEPSCs from bushy, octopus, T-stellate, and tuberculoventral cells had significantly faster decay time constants (0.35-0.40 msec) than did those from fusiform and cartwheel cells (1.32-1.79 msec). Some fusiform cells had two populations of mEPSCs with distinct time courses. mEPSCs in cells with auditory nerve input alone were inhibited by philanthotoxin, a blocker of calcium-permeable AMPA receptors, whereas mEPSCs in cells with parallel fiber input were not. Thus AMPA receptors postsynaptic to the auditory nerve differ from those postsynaptic to parallel fibers both in channel-gating kinetics and in their permeability to calcium. These results confirm the conclusion that synaptic AMPA receptors are specialized according to the source of input (Hunter et al., 1993; Rubio and Wenthold, 1997; Wang et al., 1998).

Golgi cells are poised to integrate multimodal influences by participating in circuits involving granule cells in the cochlear nuclei. To understand their physiological role, intracellular recordings were made from anatomically identified Golgi cells in slices of the cochlear nuclei from mice. Cell bodies, dendrites, and terminals for all seven labeled cells were restricted to the narrow plane of the superficial granule cell domain over the ventral cochlear nucleus. The axonal arborization was the most striking feature of all Golgi cells; a dense plexus of terminals covered an area 200-400 microm in diameter in the vicinity of the cell body and dendrites. Axonal beads often surrounded granule cell bodies, indicating that granule cells are probable targets. Cells had input resistances up to 130 M omega and fired regular, overshooting action potentials. Golgi cells probably receive auditory nerve input, because shocks to the cut end of the auditory nerve excited Golgi cells with excitatory postsynaptic potentials (EPSPs). The latency of EPSPs shortened to a minimum and the amplitude of EPSPs grew in several steps as the strength of shocks was increased. The minimum latency of EPSPs in Golgi cells was on average 1.3 milliseconds, 0.6 milliseconds longer than the minimum latencies of EPSPs in nearby octopus and T stellate cells. The long latency raises the possibility that Golgi cells receive input from slowly conducting, unmyelinated auditory nerve fibers. Golgi cells are also excited by interneurons with N-methyl-D-aspartate receptors, probably granule cells, because repetitive shocks and single shocks in the absence of extracellular Mg2+ evoked late EPSPs that were reversibly blocked by DL-2-amino-5-phosphono-valeric acid.

Several animals have been used as models for experimental upper urinary tract surgery. Although minipigs have recently gained favor because their upper urinary tract is grossly similar to that of humans, the ureteral microanatomic features of the two species have not been compared. We evaluated the histologic features of human and animal ureters in order to provide addition information regarding experimental models for upper urinary tract surgery. Cross-sections of upper, middle, and lower ureteral segments from human autopsy specimens and animals (farm pig, minipig, dog, sheep, rabbit, and rat) were evaluated after preparation with Masson's trichrome stain. Morphology, computer-assisted morphometry, linear micrometry, and point-count estimation of smooth muscle/connective tissue ratios were assessed. The epithelium was remarkably consistent across all species, both morphologically and in terms of absolute size. The lamina propria was highly vascularized in all species, but the compactness varied with the overall ureteral dimensions. In the muscularis, the relative size and the percentage composed of smooth muscle differed widely among species, as did the ratio of muscularis to lamina propria cross-sectional surface area. Among the species evaluated, the sheep, farm pig, and minipig ureters were the best histologic approximations of the human ureter. Given the difficulties with manipulation of the small sheep ureter, the minipig and farm pig models appear to be optimal for experimental research on upper urinary tract surgery by an endourologic approach.

Purpose: The duration of stenting after endoureterotomy is a controversial issue. An even more basic question, however, is whether stent placement is needed at all. We performed a porcine study to address this question., Methods: A unilateral midureteral stricture was created in 20 minipigs. Six weeks later, 15 pigs underwent endoureterotomy. In 10 animals, a 7F ureteral stent was placed for 1 week. Five pigs remained unstented. Three months later, all 20 ureters were studied radiographically and were harvested., Results: Three of 5 control animals and 2 of 10 stented animals has strictures. In the unstented study group, all 5 animals had a nonobstructing dilation at the site of endoureterotomy. This was corroborated by a normal furosemide washout renal scan in all 3 animals so tested., Conclusions: The result of unstented endoureterotomy in the porcine model suggests that, after endoureterotomy of secondary midureteral strictures, stenting may be unnecessary.

At this point in time, endopyelotomy is first-line therapy for both primary and secondary adult ureteropelvic junction obstruction (UPJO) in many medical centers. However, the potential, albeit small, for significant bleeding with any endoincision of the UPJ has sparked interest in the simple, less morbid technique of endoballoon rupture. To date, no comparative data are available on the effectiveness of these two techniques. Thirty female minipigs were randomized to cutting balloon (Acucise) endopyelotomy (AEP) (N = 13), endoballoon rupture (EBR) (N = 13), or a control arm (N = 4). Following baseline retrograde pyelogram (RPG) and diuretic renogram (DRG), a secondary proximal ureteral stricture was created by laparoscopic ligation of the UPJ. After 8 weeks, AEP or EBR was performed in each of the study pigs. In 16 pigs (8 AEP, 8 EBR), a 7F 22-cm ureteral stent was placed (chronic arm). After 6 weeks, the stent was removed, and a second RPG and DRG were performed. Three months post-treatment, after RPG and DRG, the renal units were harvested, and histologic sections of the affected UPJ, contralateral normal ureter, and ipsilateral kidney were examined. Ten pigs (5 AEP, 5 EBR) underwent harvest immediately after treatment (acute arm). The four control animals remained untreated. At 8 weeks, all minipigs had obstructive findings on RPG and DRG. All UPJs could be treated but one, which had an impassable stricture; there were no perioperative complications. In the acute arm, all UPJs were patent. All five AEP ureters had evidence of an uneven cut and cautery effect. Of the EBR ureters, two had smooth tears and three had ragged tears, and none had evidence of cautery effect. In the chronic arm, 3 months after either AEP or EBR, all minipigs had a patent UPJ, yet only 5 of 16 had an improved 1 1/2 by DRG. Histologic sections of the affected UPJs from 20 minipigs in the chronic arm (8 AEP, 8 EBR, 4 controls) were indistinguishable among the three groups; each revealed significant periureteral fibrosis and chronic inflammation with a mainly unremarkable muscular layer. However, histologic sections of 25 treated kidneys, including both acute and chronic animals (13 AEP, 12 EBR), revealed endstage renal disease (N = 10), chronic inflammatory changes (N = 7), or normal tissue (N = 8). Again, there was no trend favoring either AEP and EBR. In summary, in this laboratory study, we could detect no difference in outcome between an incisional endopyelotomy and an endoballoon rupture for treating secondary UPJO.

Twelve female microminipigs with normal bladder capacity underwent laparoscopic bladder seromyotomy. Three other female microminipigs were added to the study as controls. Urodynamic studies and cystograms were performed preoperatively and at 2 and 4 months after a laparoscopic bladder seromyotomy. Histologic studies of the treated bladders were performed when the animals were euthanized at 4 months. The operation was completed in all 12 test animals. There was no significant difference in bladder capacity or leak-point pressure between the 12 seromyotomy and the 3 control bladders at any time point. Histologically, over the seromyotomy site, the urothelium remained intact; however, the muscularis was attenuated, and a thin layer of fibrotic tissue replaced the normal serosal covering of the bladder. Laparoscopic bladder seromyotomy can be performed reliably in the porcine animal model. Not surprisingly, no significant changes in bladder capacity or bladder compliance were seen in our study of normal bladders. An animal model of a neuropathic contracted bladder is needed to assess more accurately the physiological impact of laparoscopic seromyotomy.

Objectives: To ascertain whether insertion of a ureteral stent improves the outcome of middle ureteral (overlying the pelvic bone) stones treated with extracorporeal shock-wave lithotripsy (ESWL)., Methods: Thirty-three patients with middle ureteral stones were treated with ESWL at our institution between October 1991 and October 1994. Twenty-six patients were available for follow-up; 14 patients were treated with stent bypass, 8 were treated in situ, and 4 patients were treated after percutaneous nephrostomy (PCN). All patients were treated initially on an unmodified Dornier HM-3, and all but 4 patients were treated in the prone position on a modified Stryker frame. Follow-up consisted of a plain abdominal radiograph, intravenous urogram, occasionally a retrograde urogram, and a telephone interview., Results: The overall stone-free rate for ESWL alone was 73%, and the efficiency quotient was 69. The stone-free rates after a single treatment for the stent bypass, in situ, and PCN groups were 71%, 63%, and 75%, respectively. Overall, 4% of patients required retreatment, 19% of patients required an auxiliary procedure, and 8% of the patients required hospital or emergency room admissions for renal colic. For stones 10 mm or greater (9), stone-free rates after one treatment for the stent bypass, in situ, and PCN groups were 33%, 33%, and 67%, respectively; for stones less than 10 mm (17), success rates were 82%, 80%, and 100%, respectively., Conclusions: Pretreatment stinting provides no advantage over in situ ESWL for middle ureteral calculi (Fisher's exact test, P = 1.0). ESWL is a reasonable initial therapy for middle ureteral stones less than 10 mm.

Obtaining a precise fascial closure of larger laparoscopic port sites presents an ongoing challenge for even the most experienced laparoscopic surgeons. To this end, we evaluated five new methods for closing laparoscopic port sites and compared these with the standard technique of a hand-sutured repair using a 0 absorbable suture in the pig. The new devices studied were the Carter-Thomason Needle-Point Suture Passer (CTNSP), the eXit Disposable Puncture Closure (EDPC) device, the Maciol suture needle (MSN) set, the Endoclose suture carrier, and a nonpropreitary technique using a long 14-gauge Angiocatheter and a looped Prolene suture. Unlike the typical clinical situation, the fascia of the pig lies extremely close to the skin; hence, the sutured closure could be routinely performed most quickly of all. Among the newer techniques, the CTNSP provided the quickest closure. The Endoclose, MSN, and 14-gauge Angiocatheter techniques required the use of an auxiliary grasper, which appeared to slow the closure. Only the EDPC provided an airtight closure in 100% of cases. Of the new techniques, the 14-gauge Angiocatheter technique was the least expensive ($3). The efficacy of these techniques in the clinical realm needs to be assessed by a randomized trial.

Purpose: To study the acute and chronic tissue effects of using high pressure CO2 to dissect tissues during laparoscopic procedures., Materials and Methods: A 5-mm. laparoscopic pneumodissector, capable of delivering brief bursts of high pressure CO2 (20 to 100 psi), was discharged on a variety of porcine tissues including the renal hilum. Acute and chronic histological sections, intraoperative blood gases and perioperative renal scans were obtained., Results: The only tissue with significant acute damage was the spleen. Acute changes in other tissues were minimal; long-term studies revealed no discernible damage to these same tissues. Intraoperative blood gases revealed no significant changes in the serum pCO2 or pH. Likewise, there was no renal damage discernible by renal scans., Conclusions: Pneumodissection at 50 psi is a safe method for dissecting the porcine kidney and the vessels of the renal hilum. Clinical studies are pending.

The stent size necessary to promote optimal ureteral healing after an endoureterotomy is not known. We compared healing of an endoureterotomy over a 7F indwelling ureteral stent with healing over a 14F endopyelotomy stent. A midureteral stricture was created in each of 25 anesthetized female minipigs using an electrified stone basket passed retrograde. Six weeks later, the stricture was incised with a 24F cutting balloon device. Twenty pigs were randomized to receive a 7F or a 14F stent; four control pigs received neither incisions nor stents. At 1 week, a radiograph was performed to confirm proper stent position, and the stents were removed. At 3 months, a retrograde ureterogram was performed, and the ureters were examined grossly and harvested for histologic studies. Two of the ten pigs in each study group developed a recurrent stricture. The use of a 14F stent provided no advantage over the use of a smaller, more easily positioned 7F stent.

Excellent results and durable success have been achieved with antegrade and retrograde endo-pyelotomy for treating primary and secondary ureteropelvic junction obstruction. Recently, a 30F dilating balloon was used to rupture the ureteropelvic junction (ENDOBRST) with encouraging results. While balloon distention of the ureteropelvic junction is a technically simpler procedure than endo-pyelotomy, clinical and laboratory data comparing the 2 methods are lacking. In an acute and chronic animal study we compared endo-pyelotomy via a ureteral cutting balloon incision to balloon rupture (that is 30F) of the normal ureteropelvic junction in each of 20 female farm pigs. Eight pigs were harvested acutely after treatment, and a macroscopic and histological examination of the treated ureteropelvic junction was completed. In 11 chronic pigs after endo-pyelotomy a 7F double pigtail ureteral stent was placed bilaterally and then removed after 6 weeks. Evaluation in the chronic group consisted of a furosemide washout renogram and retrograde pyelogram immediately preoperatively and 6 weeks after stent removal. The animals were likewise harvested 6 weeks after stent removal. One control pig underwent passage of the balloon cutting catheter and balloon dilating catheters without activation or dilation, respectively. Ureteral stents were placed bilaterally for 6 weeks and the pig was otherwise treated similarly to the other chronic study animals. In the acute group all ureters after endo-pyelotomy demonstrated retroperitoneal extravasation of contrast material. At harvest the ureters had been cleanly incised along a length of 3 to 4 cm. through the adventitial layer. In contrast, the balloon treated ureters showed free retroperitoneal extravasation in only half of the animals. Among the balloon treated ureters 7 of 8 had a linear tear of varying length (1 to 5 cm.) involving all but a thin adventitial layer of tissue. Histologically, the endo-pyelotomy ureters demonstrated a clean, linear transmural incision with virtually no destruction of surrounding tissue in 6 cases. In the remaining 2 cases an incision into but not completely through the muscular layer was observed. The balloon treated ureters showed a perforation through the muscular wall in 7 cases. However, periureteral hemorrhage and urothelial loss were common findings. In the chronic group infection and continued urine extravasation from the endo-pyelotomy site resulted in a 45% mortality rate. Of the surviving 6 pigs 83% of the balloon treated and 67% of the endo-pyelotomy pigs had a patent ureteropelvic junction by retrograde pyelogram and renogram. Histologically, the 2 sides were indistinguishable, with both showing mild fibrosis and chronic inflammation.(ABSTRACT TRUNCATED AT 400 WORDS)

We investigated whether variations in alertness among individuals with profound multiple disabilities affected subsequent responsiveness to training programs. Three experiments were conducted involving 5 people. In Experiment 1, results indicated that alertness of 3 individuals increased with provision of skill-acquisition training programs. Results also indicated no predictive relationship between alertness levels prior to training and subsequent responsiveness to training. Experiment 2 replicated results of Experiment 1 with 2 participants from Experiment 1 and an additional participant. Results of Experiment 2 also indicated that the increased alertness levels accompanying provision of training were not a function of the participants simply being in an inactive environment prior to training. Results of Experiment 3 indicated that alertness of an additional participant increased through provision of another training intervention, involving a systematic preference assessment. Responses during the preference assessment appeared to be unrelated to previously existing alertness levels. These findings suggest the need for caution when considering the withholding of scheduled training because an individual appears to be nonalert.