Exploring Nursing Students' Experiences With Different Teaching Pedagogies: A Mixed-Methods Study.

BACKGROUND: Educational methods continue to evolve to meet the challenge of teaching undergraduate nursing students. Innovative teaching pedagogies require nursing students to be actively involved in their own learning compared with traditional didactical styles. METHOD: Students were exposed to three distinct teaching pedagogies: inquiry-based, online, and educator-led during their second year of study. Students' learning preferences were explored using a mixed-methods approach. Quantitative data were collected using an online questionnaire, followed by a focus group interview. RESULTS: The quantitative data revealed students preferred being taught directly from educators rather than through self-directed and online study. Manifest content analysis of qualitative data revealed four categories that supported student learning and five categories that hindered student learning. CONCLUSION: Students struggled when required to be self-directed in their learning. Students reported feeling uncertain and overwhelmed initially, which highlighted the importance of strong social and academic support to facilitate effective learning. [J Nurs Educ. 2022;61(3):147-152.].

Pharmacological inhibition of STriatal-Enriched protein tyrosine Phosphatase by TC-2153 reduces hippocampal excitability and seizure propensity.

OBJECTIVE: STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase. Membrane-bound STEP61 is the only isoform expressed in hippocampus and cortex. Genetic deletion of STEP enhances excitatory synaptic currents and long-term potentiation in the hippocampus. However, whether STEP61 affects seizure susceptibility is unclear. Here we investigated the effects of STEP inhibitor TC-2153 on seizure propensity in a murine model displaying kainic acid (KA)-induced status epilepticus and its effect on hippocampal excitability. METHODS: Adult male and female C57BL/6J mice received intraperitoneal injection of either vehicle (2.8% dimethylsulfoxide [DMSO] in saline) or TC-2153 (10 mg/kg) and then either saline or KA (30 mg/kg) 3 h later before being monitored for behavioral seizures. A subset of female mice was ovariectomized (OVX). Acute hippocampal slices from Thy1-GCaMP6s mice were treated with either DMSO or TC-2153 (10 µM) for 1 h, and then incubated in artificial cerebrospinal fluid (ACSF) and potassium chloride (15 mM) for 2 min prior to live calcium imaging. Pyramidal neurons in dissociated rat hippocampal culture (DIV 8-10) were pre-treated with DMSO or TC-2153 (10 µM) for 1 h before whole-cell patch-clamp recording. RESULTS: TC-2153 treatment significantly reduced KA-induced seizure severity, with greater trend seen in female mice. OVX abolished this TC-2153-induced decrease in seizure severity in female mice. TC-2153 application significantly decreased overall excitability of acute hippocampal slices from both sexes. Surprisingly, TC-2153 treatment hyperpolarized resting membrane potential and decreased firing rate, sag voltage, and hyperpolarization-induced current (Ih ) of cultured hippocampal pyramidal neurons. SIGNIFICANCE: This study is the first to demonstrate that pharmacological inhibition of STEP with TC-2153 decreases seizure severity and hippocampal activity in both sexes, and dampens hippocampal neuronal excitability and Ih . We propose that the antiseizure effects of TC-2153 are mediated by its unexpected action on suppressing neuronal intrinsic excitability.

Evaluation of optimal treatment for urinary tract infections in outpatient clinics at an academic medical center: Opportunities for antimicrobial stewardship.

Outpatient empiric urinary tract infection (UTI) prescribing is an area of interest for antimicrobial stewardship efforts. We conducted a retrospective chart review evaluating optimal antibiotic prescribing for UTIs in our internal medicine and urology clinics and found significant differences in prescribing patterns between provider type and UTI category. These data will inform our antimicrobial stewardship efforts in these clinics.

Basolateral amygdala corticotropin-releasing factor receptor type 1 regulates context-cocaine memory strength during reconsolidation in a sex-dependent manner.

The basolateral amygdala (BLA) is a critical brain region for cocaine-memory reconsolidation. Corticotropin-releasing factor receptor type 1 (CRFR1) is densely expressed in the BLA, and CRFR1 stimulation can activate intra-cellular signaling cascades that mediate memory reconsolidation. Hence, we tested the hypothesis that BLA CRFR1 stimulation is necessary and sufficient for cocaine-memory reconsolidation. Using an instrumental model of drug relapse, male and female Sprague-Dawley rats received cocaine self-administration training in a distinct environmental context over 10 days followed by extinction training in a different context over 7 days. Next, rats were re-exposed to the cocaine-paired context for 15 min to initiate cocaine-memory retrieval and destabilization. Immediately or 6 h after this session, the rats received bilateral vehicle, antalarmin (CRFR1 antagonist; 500 ng/hemisphere), or corticotropin-releasing factor (CRF; 0.2, 30 or 500 ng/hemisphere) infusions into the BLA. Resulting changes in drug context-induced cocaine seeking (index of context-cocaine memory strength) were assessed three days later. Female rats self-administered more cocaine infusions and exhibited more extinction responding than males. Intra-BLA antalarmin treatment immediately after memory retrieval (i.e., when cocaine memories were labile), but not 6 h later (i.e., after memory reconsolidation), attenuated drug context-induced cocaine seeking at test independent of sex, relative to vehicle. Conversely, intra-BLA CRF treatment increased this behavior selectively in females, in a U-shaped dose-dependent fashion. In control experiments, a high (behaviorally ineffective) dose of CRF treatment did not reduce BLA CRFR1 cell-surface expression in females. Thus, BLA CRFR1 signaling is necessary and sufficient, in a sex-dependent manner, for regulating cocaine-memory strength.

Heterocyclic group transfer reactions with I(iii) N-HVI reagents: access to N-alkyl(heteroaryl)onium salts via olefin aminolactonization.

Pyridinium and related N-alkyl(heteroaryl)onium salts are versatile synthetic intermediates in organic chemistry, with applications ranging from ring functionalizations to provide diverse piperidine scaffolds to their recent emergence as radical precursors in deaminative cross couplings. Despite their ever-expanding applications, methods for their synthesis have seen little innovation, continuing to rely on a limited set of decades old transformations and a limited subset of coupling partners. Herein, we leverage (bis)cationic nitrogen-ligated I(iii) hypervalent iodine reagents, or N-HVIs, as "heterocyclic group transfer reagents" to provide access to a broad scope of N-alkyl(heteroaryl)onium salts via the aminolactonization of alkenoic acids, the first example of engaging an olefin to directly generate these salts. The reactions proceed in excellent yields, under mild conditions, and are capable of incorporating a broad scope of sterically and electronically diverse aromatic heterocycles. The N-HVI reagents can be generated in situ, the products isolated via simple trituration, and subsequent derivatizations demonstrate the power of this platform for diversity-oriented synthesis of 6-membered nitrogen heterocycles.

Acetyl-l-carnitine does not prevent neurodegeneration in a rodent model of prolonged neonatal anesthesia.

Many studies have shown that prolonged or repeated use of general anesthesia early in life can cause an increase in neurodegeneration and lasting changes in behavior. While short periods of general anesthesia appear to be safe, there is a concern about the neurotoxic potential of prolonged or repeated general anesthesia in young children. Unfortunately, the use of general anesthesia in children cannot be avoided. It would be a great benefit to develop a strategy to reduce or reverse anesthesia mitigated neurotoxicity. The mechanisms behind anesthesia related neurotoxicity are unknown, but evidence suggests that mitochondrial dysfunction and abnormal energy utilization are involved. Recent research suggests that a class of compounds known as carnitines may be effective at preventing anesthesia related neurotoxicity by influencing fatty acid metabolism in the mitochondria. However, it is unknown if carnitines can provide protection against changes in behavior associated with early life exposure to anesthesia. Accordingly, we evaluated the neuroprotective potential of acetyl-l-carnitine in 7-day old rats. Rat pups were exposed to 6 h of general anesthesia with sevoflurane or a control condition, with and without acetyl-l-carnitine. The oxygenation level of animals was continuously monitored during sevoflurane exposure, and any animal showing signs of hypoxia was removed from the study. Animals exposed to sevoflurane showed clear signs of neurodegeneration 2 h after sevoflurane exposure. The hippocampus, cortex, thalamus, and caudate putamen all had elevated levels of Fluoro-Jade C staining. Despite the elevated levels of Fluoro-Jade C, few behavioral changes were observed in an independent cohort of animals treated with sevoflurane. Furthermore, acetyl-l-carnitine had little impact on levels of Fluoro-Jade C staining in animals treated with sevoflurane. These data suggest that acetyl-l-carnitine may offer little protection again anesthesia related neurotoxicity in fully oxygenated animals.

Regions of the basal ganglia and primary olfactory system are most sensitive to neurodegeneration after extended sevoflurane anesthesia in the perinatal rat.

Extended general anesthesia early in life is neurotoxic in multiple species. However, little is known about the temporal progression of neurodegeneration after general anesthesia. It is also unknown if a reduction in natural cell death, or an increase in cell creation, occurs as a form of compensation after perinatal anesthesia exposure. The goal of this study was to evaluate markers of neurodegeneration and cellular division at 2, 24, or 72 h after sevoflurane (Sevo) exposure (6 h) in fully oxygenated postnatal day (PND) 7 rats. Neurodegeneration was observed in areas throughout the forebrain, while the largest changes (fold increase above vehicle) were observed in areas associated with either the primary olfactory learning pathways or the basal ganglia. These regions included the indusium griseum (IG, 25-fold), the posterior dorso medial hippocampal CA1 (17-fold), bed nucleus of the stria terminalis (Bed Nuclei STM, 5-fold), the shell of the nucleus accumbens (Acb, 5-fold), caudate/putamen (CPu, 5-fold), globus pallidus (GP, 9-fold) and associated thalamic (11-fold) and cortical regions (5-fold). Sevo neurodegeneration was minimal or undetectable in the ventral tegmentum, substantia nigra, and most of the hypothalamus and frontal cortex. In most brain regions where neurodegeneration was increased 2 h post Sevo exposure, the levels returned to <4-fold above control levels by 24 h. However, in the IG, CA1, GP, anterior thalamus, medial preoptic nucleus of the hypothalamus (MPO), anterior hypothalamic area (AHP), and the amygdaloid nuclei, neurodegeneration at 24 h was double or more than that at 2 h post exposure. Anesthesia exposure causes either a prolonged period of neurodegeneration in certain brain regions, or a distinct secondary degenerative event occurs after the initial insult. Moreover, regions most sensitive to Sevo neurodegeneration did not necessarily coincide with areas of new cell birth, and new cell birth was not consistently affected by Sevo. The profile of anesthesia related neurotoxicity changes with time, and multiple mechanisms of toxicity may exist in a time-dependent fashion.

Population structure and genetic diversity of Trichomonas vaginalis clinical isolates in Australia and Ghana.

Population genetic studies of Trichomonas vaginalis have detected high genetic diversity associated with phenotypic differences in clinical presentations. In this study, microscopy and next generation-multi-locus sequence typing (NG-MLST) were used to identify and genetically characterise T. vaginalis isolates from patients in Australia and Ghana. Seventy-one polymorphic nucleotide sites, 36 different alleles, 48 sequence types, 24 of which were novel, were identified among 178 isolates, revealing a geneticallly diverse T. vaginalis population. Polymorphism was found at most loci, clustering genotypes into eight groups among both Australian and Ghanaian isolates, although there was some variation between countries. The number of alleles for each locus ranged from two to nine. Study results confirmed geographic expansion and diversity of the T. vaginalis population. Two-type populations in almost equal frequencies and a third unassigned group were identified in this study. Linkage disequilibrium was observed, suggesting T. vaginalis population is highly clonal. Multillocus disequilibrium was observed even when analysing clades separately, as well as widespread clonal genotypes, suggesting that there is no evidence of recent recombination. A more comprehensive study to assess the extent of genetic diversity and population structure of T. vaginalis and their potential impact on varied pathology observed among infected individuals is recommended.

Polycystin 2 is increased in disease to protect against stress-induced cell death.

Polycystin 2 (PC2 or TRPP1, formerly TRPP2) is a calcium-permeant Transient Receptor Potential (TRP) cation channel expressed primarily on the endoplasmic reticulum (ER) membrane and primary cilia of all cell and tissue types. Despite its ubiquitous expression throughout the body, studies of PC2 have focused primarily on its role in the kidney, as mutations in PC2 lead to the development of autosomal dominant polycystic kidney disease (ADPKD), a debilitating condition for which there is no cure. However, the endogenous role that PC2 plays in the regulation of general cellular homeostasis remains unclear. In this study, we measure how PC2 expression changes in different pathological states, determine that its abundance is increased under conditions of cellular stress in multiple tissues including human disease, and conclude that PC2-deficient cells have increased susceptibility to cell death induced by stress. Our results offer new insight into the normal function of PC2 as a ubiquitous stress-sensitive protein whose expression is up-regulated in response to cell stress to protect against pathological cell death in multiple diseases.

Development and Validation of the Performance-Based Situation Awareness Observation Schedule (PBSAOS): The Process and Lessons Learned.

BACKGROUND: No instruments are currently available to assess nursing students' maintenance of situation awareness. The aim of this study was to develop and validate the Performance-Based Situation Awareness Observation Schedule for measuring nursing students' use of situation awareness. METHOD: Twelve expert clinicians participated in a qualitative, reiterative consensus-driven process to establish the content validity of the tool. The tool was then piloted during the delivery of a situation awareness education program for final-year nursing students. Cohen's kappa was used to assess the interrater reliability. RESULTS: The resultant tool comprised 54 items, which captured strategies to maintain situation awareness and task errors that would infer the presence of situation awareness. The values obtained for Cohen's kappa indicated that the level of agreement was at least substantial for approximately 80% of the items. CONCLUSION: This study developed a valid and reliable tool to measure nursing students' use of situation awareness. [J Nurs Educ. 2019;58(8):468-473.].

Meaningful and culturally appropriate palliative care for Chinese immigrants with a terminal condition: a qualitative systematic review protocol.

OBJECTIVE: This review aims to identify and synthesize the best qualitative evidence on the experiences of Chinese immigrants receiving palliative care in their country of residence where the culture is predominantly Western, and the experiences of their family carers. INTRODUCTION: The recent increase in international immigration has led to challenges in providing culturally appropriate palliative care. Chinese populations have particular beliefs, values and practices surrounding death and filial piety. These differ considerably from those in Western cultures and have significant implications for palliative care service provision. This review will explore the experiences and perceptions of Chinese immigrants and how their cultural beliefs shape their acceptance and decision making related to palliative care. INCLUSION CRITERIA: The review will include studies on the experiences of Chinese immigrants over 18 years of age with a terminal medical condition receiving palliative care in outpatient units, hospitals, hospices, specialist palliative care units, homes and community settings in their country of residence where the culture is predominantly Western. METHODS: Eligible studies will be studies with qualitative data including designs such as phenomenology, grounded theory, ethnography, narrative research, qualitative description, action research and feminist research published in English and Chinese. CINAHL, PsycINFO, MEDLINE, Scopus and Web of Science Core Collection will be used and grey literature will be searched using ProQuest Dissertations and Theses, OpenGrey and Caresearch. Appraisal of selected studies will be done with the Joanna Briggs Institute Qualitative Assessment and Review tool. Findings will be synthesized through a meta-aggregative approach to produce a comprehensive set of synthesized findings that can be used as a basis for evidence-based practice.

Trichomonas vaginalis infection in southern Ghana: clinical signs associated with the infection.

Trichomonas vaginalis is the causative agent for the most prevalent non-viral sexually transmitted infection (STI) among women of child-bearing age. In Ghana, although the infection is prevalent, there is a dearth of data on the risk factors and symptoms associated with T. vaginalis infection. This study was conducted on 492 women visiting gynaecological and STI clinics in the Volta Region (VR) and Greater Accra Region (GAR) in southern Ghana. Wet mount microscopy and polymerase chain reaction (PCR) were used to diagnose T. vaginalis infection. Infection prevalence was 13.2% and 18.1% by WMM and PCR, respectively. Diagnosis by PCR was significantly more sensitive (McNemar's test, p=0.0003). The regional prevalence of T. vaginalis infection by PCR was 21.7% in the VR and 12.8% in the GAR. There was a significant difference in prevalence between the two regions (Fisher's exact test, p=0.02). T. vaginalis infection was associated with vaginal itch (odds ratio [OR]=1.71, p=0.04) and a history of engaging in oral sex (OR 1.90, p=0.04). A high prevalence of T. vaginalis infection was recorded among women visiting gynaecological and STI clinics in southern Ghana. There was no consistent association of infection with any recorded clinical signs and no clear risk factors for infection were identified.

Performance based situation awareness observations in a simulated clinical scenario pre and post an educational intervention.

This study compared final year nursing students' error rate and use of strategies to maintain SA when undertaking specific nursing care in a simulated clinical environment pre and 10 weeks post a planned SA education intervention. Students were observed using a Performance Based Situation Awareness Observation Schedule (PBSAOS) undertaking two tasks in a simulated clinical environment pre and post the SA education. For task 1, post educational intervention, there was no significant increase in the error rate for any performance measures, and there were significant decreases in the error rates for three performance measures. For task 2, post educational intervention, there was a significant decrease in the error rate for two measures and a significant increase in the error rates for seven performance measures. In considering the overall group error rate when excluding uncompleted tasks, there was a significant (x = .0001) decrease in the error rate for task 1 post educational intervention (41.4% compared to 26.6%), and significant (x = 0.01) increase in the error for task 2 post educational intervention (39.6% compared to 47.3%). The findings of this study demonstrate that the implementation of an intervention designed to increase SA actually appear to have resulted in hyper-vigilance and subsequent non-completion of required tasks.

Sevoflurane exposure has minimal effect on cognitive function and does not alter microglial activation in adult monkeys.

Postoperative Cognitive Dysfunction (POCD) is a complication that has been observed in a subset of adult and elderly individuals after general anesthesia and surgery. Although the pathogenesis of POCD is largely unknown, a growing body of preclinical research suggests that POCD may be caused by general anesthesia. A significant amount of research has examined the effects of general anesthesia on neurocognitive function in rodents, yet no studies have assessed the adverse effects of general anesthesia on brain function in adult nonhuman primates. Thus, this study sought to determine the effects of an extended exposure to sevoflurane anesthesia on cognitive function and neural inflammation in adult rhesus macaques. Five adult rhesus macaques (16-17 years of age) were exposed to sevoflurane anesthesia for 8 h and, and micro-positron emission tomography (PET)/computed tomography (CT) imaging and a battery of operant tasks were used to assess the effects of anesthesia exposure on 18F-labeled fluoroethoxybenzyl-N-(4-phenoxypyridin-3-yl) acetamide ([18F]-FEPPA) uptake, a biomarker of microglia activation, and aspects of complex cognitive function. Exposure to sevoflurane anesthesia for 8 h did not increase [18F]-FEPPA uptake in the adult monkey brain. Sevoflurane anesthesia significantly decreased accuracy (mean difference = 22.79) on a learning acquisition task 6 days after exposure [t(3) = 6.92, p = 0.006], but this effect did not persist when measured 1 week and 2 weeks after additional exposures. Further, sevoflurane anesthesia had no impact on performance in 4 additional cognitive tasks. These data suggest that exposure to anesthesia alone may not be sufficient to cause persistent POCD in adult populations.

(Poly)cationic λ3-Iodane Mediated Oxidative Ring Expansion of Secondary Alcohols.

Herein, we report a simplified approach to the synthesis of medium-ring ethers through the electrophilic activation of secondary alcohols with (poly)cationic λ3-iodanes (N-HVI). Excellent levels of selectivity are achieved for C-O bond migration over established α-elimination pathways, enabled by the unique reactivity of a novel 2-OMe-pyridine-ligated N-HVI. The resulting HFIP-acetals are readily derivatized with a range of nucleophiles, providing a versatile functional handle for subsequent manipulations. The utility of this methodology for late-stage natural product derivatization was also demonstrated, providing a new tool for diversity-oriented synthesis and complexity-to-diversity (CTD) efforts. Preliminary mechanistic investigations reveal a strong effect of alcohol conformation on reactive pathway, thus providing a predictive power in the application of this approach to complex molecule synthesis.

Reduced axonal surface expression and phosphoinositide sensitivity in Kv7 channels disrupts their function to inhibit neuronal excitability in Kcnq2 epileptic encephalopathy.

Neuronal Kv7/KCNQ channels are voltage-gated potassium channels composed of Kv7.2/KCNQ2 and Kv7.3/KCNQ3 subunits. Enriched at the axonal membrane, they potently suppress neuronal excitability. De novo and inherited dominant mutations in Kv7.2 cause early onset epileptic encephalopathy characterized by drug resistant seizures and profound psychomotor delay. However, their precise pathogenic mechanisms remain elusive. Here, we investigated selected epileptic encephalopathy causing mutations in calmodulin (CaM)-binding helices A and B of Kv7.2. We discovered that R333W, K526N, and R532W mutations located peripheral to CaM contact sites decreased axonal surface expression of heteromeric channels although only R333W mutation reduced CaM binding to Kv7.2. These mutations also altered gating modulation by phosphatidylinositol 4,5-bisphosphate (PIP2), revealing novel PIP2 binding residues. While these mutations disrupted Kv7 function to suppress excitability, hyperexcitability was observed in neurons expressing Kv7.2-R532W that displayed severe impairment in voltage-dependent activation. The M518 V mutation at the CaM contact site in helix B caused most defects in Kv7 channels by severely reducing their CaM binding, K+ currents, and axonal surface expression. Interestingly, the M518 V mutation induced ubiquitination and accelerated proteasome-dependent degradation of Kv7.2, whereas the presence of Kv7.3 blocked this degradation. Furthermore, expression of Kv7.2-M518V increased neuronal death. Together, our results demonstrate that epileptic encephalopathy mutations in helices A and B of Kv7.2 cause abnormal Kv7 expression and function by disrupting Kv7.2 binding to CaM and/or modulation by PIP2. We propose that such multiple Kv7 channel defects could exert more severe impacts on neuronal excitability and health, and thus serve as pathogenic mechanisms underlying Kcnq2 epileptic encephalopathy.

The influence of situation awareness training on nurses' confidence about patient safety skills: A prospective cohort study.

BACKGROUND: Several studies report that patient safety skills, especially non-technical skills, receive scant attention in nursing curricula. Hence, there is a compelling reason to incorporate material that enhances non-technical skills, such as situation awareness, in nursing curricula in order to assist in the reduction of healthcare related adverse events. OBJECTIVES: The objectives of this study were to: 1) understand final year nursing students' confidence in their patient safety skills; and 2) examine the impact of situation awareness training on final year nursing students' confidence in their patient safety skills. METHODS: Participants were enrolled from a convenience sample comprising final year nursing students at a Western Australia university. Self-reported confidence in patient safety skills was assessed with the Health Professional in Patient Safety Survey before and after the delivery of a situation awareness educational intervention. Pre/post educational intervention differences were examined by repeated measures ANOVA. RESULTS: No significant differences in confidence about patient safety skills were identified within settings (class/clinical). However, confidence in patient safety skills significantly decreased between settings i.e. nursing students lost confidence after clinical placements. CONCLUSION: The educational intervention delivered in this study did not seem to improve confidence in patient safety skills, but substantial ceiling effects may have confounded the identification of such improvement. Further studies are required to establish whether the findings of this study can be generalised to other university nursing cohorts.

Preventing, Identifying, and Treating Prescription Drug Misuse Among Active-Duty Service Members.

Prescription drug misuse (PDM) is of critical concern for the military because of its potential impact on military readiness, the health and well-being of military personnel, and associated health care costs. The purpose of this study is to summarize insights gleaned from a series of activities that the RAND Corporation undertook for the Deputy Assistant Secretary of Defense for Readiness to address this important health and military readiness issue. The authors completed a review of U.S. Department of Defense policies and a comprehensive literature review of clinical guidelines and the empirical literature on the prevention and treatment of PDM and conducted individual face-to-face interviews with 66 health and behavioral health care providers at nine medical treatment facilities across three regions within the contiguous United States to identify best practices in the prevention, identification, and treatment of PDM and the extent to which those practices are known and followed. The study also presents the framework of an analytic tool that, once informed by data available to the military but not available to the authors, can assist the military in predicting future trends in PDM based on current demographics of active-duty service members and rates of injury and prescribing of prescription drugs. The findings from this work led the authors to formulate a set of key insights that they believe might improve the rapid identification and treatment of service members dealing with PDM, thereby improving future force readiness.

Review of preclinical studies on pediatric general anesthesia-induced developmental neurotoxicity.

Thousands of infants and children undergo complicated surgical procedures that require prolonged periods of anesthesia and/or sedation each year. A growing body of preclinical research suggests pediatric anesthetics are harmful to the developing brain; yet, the extent to which these effects generalize to the clinical setting remains unclear. As there will be a continuing need for surgical and other interventions requiring sedation and/or anesthesia during the neonatal period, it seems clear that research efforts should focus on determining the extent to which general anesthetics can affect the developing brain as well as determining strategies for preventing or ameliorating the adverse effects associated with exposure to such agents. The purpose of this paper is to provide a review of the preclinical literature examining the effects of general anesthesia on brain and behavioral development. This paper will detail the effects of different anesthetic agents on various indices of neurotoxicity and functional outcomes as well as provide a review of potential protective compounds and suggestions for areas of future research.

Single and repeated exposures to the volatile anesthetic isoflurane do not impair operant performance in aged rats.

Postoperative Cognitive Dysfunction (POCD) is a complication that can occur in the elderly after anesthesia and surgery and is characterized by impairments in information processing, memory, and executive function. Currently, it is unclear whether POCD is due to the effects of surgery, anesthesia, or perhaps some interaction between these or other perioperative variables. Studies in rodents suggest that the development of POCD may be related directly to anesthesia-induced neuroactivity. Volatile anesthetics have been shown to increase cellular inflammation and apoptosis within the hippocampus of aged rodents, while producing corresponding impairments in hippocampal-dependent brain functions. However, it is unclear whether volatile anesthetics can affect additional aspects of cognition that do not primarily depend upon the hippocampus. The purpose of this study was to use established operant tests to examine the effects of isoflurane on aspects of behavioral inhibition, learning, and motivation in aged rats. Twenty-one adult Sprague-Dawley rats (11 male, 10 female) were trained to perform fixed consecutive number (FCN), incremental repeated acquisition (IRA), and progressive ratio (PR) tasks for a minimum of 15 months prior to receiving anesthesia. At 23 months of age, rats were exposed to 1.3% isoflurane or medical grade air for 2h. Initial results revealed that a 2h exposure to isoflurane had no effect on IRA, FCN, or PR performance. Thus, rats received 3 additional exposures to 1.3% isoflurane or medical grade air: 2, 4 and 6h exposures with 2 weeks elapsing before exposure two, 3 weeks elapsing between exposures two and three, and 2 weeks elapsing between exposures three and four. These additional exposures had no observable effects on performance of any operant task. These results suggest that single and repeated exposures to isoflurane do not impair the performance of aged rats in tasks designed to measure behavioral inhibition, learning, and motivation. This lack of significant effect suggests that the impairments associated with isoflurane exposure may not generalize to all aspects of cognition, but may be selective to tasks that primarily measure spatial memory processes.