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Novelty and appropriateness are two fundamental components of creativity. However, the way in which novelty and appropriateness are separated at behavioral and neural levels remains poorly understood. In the present study, we aim to distinguish behavioral and neural bases of novelty and appropriateness of creative idea generation. In alignment with two established theories of creative thinking, which respectively, emphasize semantic association and executive control, behavioral results indicate that novelty relies more on associative abilities, while appropriateness relies more on executive functions. Next, employing a connectome predictive modeling (CPM) approach in resting-state fMRI data, we define two functional network-based models-dominated by interactions within the default network and by interactions within the limbic network-that respectively, predict novelty and appropriateness (i.e., cross-brain prediction). Furthermore, the generalizability and specificity of the two functional connectivity patterns are verified in additional resting-state fMRI and task fMRI. Finally, the two functional connectivity patterns, respectively mediate the relationship between semantic association/executive control and novelty/appropriateness. These findings provide global and predictive distinctions between novelty and appropriateness in creative idea generation., (© 2024. The Author(s).)

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease and its influence on drug-induced liver injury (DILI) is not fully understood. We investigated whether NAFLD can influence acetaminophen (APAP [N-acetyl-p-aminophenol])-induced hepatotoxicity in a diet-induced obese (DIO) mouse model of NAFLD. The male C57BL/6NTac DIO mice, fed a high-fat diet for more than 12 weeks, developed obesity, hyperinsulinemia, impaired glucose tolerance, and hepatomegaly with hepatic steatosis, similar to human NAFLD. In the acute toxicity study after a single dose of APAP (150 mg/kg), compared with control lean mice, the DIO mice had decreased serum transaminase levels and less severe hepatocellular injury. The DIO mice also had altered expression of genes related to APAP metabolism. Chronic APAP exposure for 26 weeks did not predispose the DIO mice with NAFLD to more severe hepatotoxicity compared with the lean mice. These results suggested that the C57BL/6NTac DIO mouse model appears to be more tolerant to APAP-induced hepatotoxicity than lean mice, potentially related to altered xenobiotic metabolizing capacity in the fatty liver. Further mechanistic studies with APAP and other drugs in NAFLD animal models are necessary to investigate the mechanism of altered susceptibility to intrinsic DILI in some human NAFLD patients.

Introduction: Reasoning is a complex form of human cognition whose nature has long been debated. While a number of neurocognitive mechanisms for deductive reasoning have been offered, one of the most prominent accounts is Mental Model Theory (MMT). According to MMT, humans are able to manipulate and represent information for reasoning and problem solving by leveraging the brain's evolved visuospatial resources. Thus, when solving deductive reasoning problems, reasoners build "mental models" of the essential pieces of information conveyed in the premises, with their relations to each other represented spatially-even when the information contained within a reasoning problem is not intrinsically spatial. Crucially, taking a spatially-based approach, such as building mental models, supports higher accuracy on deductive reasoning problems. However, no study has empirically tested whether explicitly training this mental modeling ability leads to improved deductive reasoning performance., Method: Therefore, we designed the Mental Models Training App, a cognitive training mobile application which requires participants to complete increasingly difficult reasoning problems while using an external mental modeling tool. In this preregistered study (https://osf.io/4b7kn), we conducted a between-subjects experiment ( N = 301) which compared the Mental Models Training App to 3 distinct control conditions in order to examine which specific components (if any) of the training were causally responsible for improved reasoning performance., Results: Results demonstrate that, when compared to a passive control condition, the Mental Models Training App led to improvements in adults' verbal deductive reasoning performance both during and after the training intervention. However, contrary to our preregistered hypotheses, the training-induced improvements were not significantly larger than the effects of the active control conditions-one which included adaptive practice of the reasoning problems, and one which included adaptive practice as well as a spatial alphabetization control task., Discussion: Therefore, while the present results demonstrate the ability of the Mental Models Training App to enhance verbal deductive reasoning, they do not support the hypothesis that directly training participants mental modeling ability yields improved performance beyond the effects of adaptive practice of reasoning. Future research should examine the long-term effects of repeated usage of the Mental Models Training App, as well as transfer effects to other forms of reasoning. Finally, we present the Mental Models Training App as a free mobile application available on the Apple App store (https://apps.apple.com/us/app/mental-models-training/id1664939931), in the hope that this translational research may be utilized by the general public to improve their reasoning ability., Competing Interests: RC and AG are the developers of intellectual property owned by Georgetown University related to the Mental Models Training App technology that is described in this manuscript. Although the app is free to download, it includes advertisements and in-app purchases that have the potential to generate revenue for RC, AG, and Georgetown University. Google manages all aspects of the advertisements including content and placement. Furthermore, in-app advertisements do not necessarily represent the data presented in the app. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cortes, Weinberger and Green.)

Current debate surrounds the promise of neuroscience for education, including whether learning-related neural changes can predict learning transfer better than traditional performance-based learning assessments. Longstanding debate in philosophy and psychology concerns the proposition that spatial processes underlie seemingly nonspatial/verbal reasoning (mental model theory). If so, education that fosters spatial cognition might improve verbal reasoning. Here, in a quasi-experimental design in real-world STEM classrooms, a curriculum devised to foster spatial cognition yielded transfer to improved verbal reasoning. Further indicating a spatial basis for verbal transfer, students' spatial cognition gains predicted and mediated their reasoning improvement. Longitudinal fMRI detected learning-related changes in neural activity, connectivity, and representational similarity in spatial cognition-implicated regions. Neural changes predicted and mediated learning transfer. Ensemble modeling demonstrated better prediction of transfer from neural change than from traditional measures (tests and grades). Results support in-school "spatial education" and suggest that neural change can inform future development of transferable curricula.

Extensive evidence and theory suggest that the development of motor skills during infancy and early childhood initiates a "developmental cascade" for cognitive abilities, such as reading and math. Motor skills are closely connected with the development of spatial cognition, an ability that supports deductive reasoning. Despite the linkage between motor skills and spatial cognition, and spatial cognition with deductive reasoning, no research has explored the developmental connection between early motor skills and reasoning ability, a plausible pathway through which the developmental cascade operates. Drawing data from the 1970 British Cohort Study (N = 1,233; 95% British, 5% other race/ethnicity; 54% male, 46% female; 7% low income, 80% middle income, 12% high income), this study investigated whether there was a relationship between gross and fine motor skills in infancy (22 months of age) and early childhood (42 months of age) and visuospatial deductive reasoning in adolescence (at 10 and 16 years of age). Results indicated that fine but not gross motor skills during early childhood positively predicted reasoning in adolescence. Critically, the fine motor-reasoning association mediated the previously observed link between early fine motor skills and adolescent reading and math ability. These results deepen our understanding of developmental cascade theory and mental model theory by identifying visuospatial reasoning (i.e., mental modeling) as a potential mechanism through which motor skills initiate cognitive development and academic success in reading and math. These findings also highlight the importance of early intervention programs targeting motor skills and illuminate the impact of those interventions on later cognitive and academic skills. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Creative cognition has been consistently associated with functional connectivity between frontoparietal control and default networks. However, recent research identified distinct connectivity dynamics for subnetworks within the larger frontoparietal system-one subnetwork (FPCNa) shows positive coupling with the default network and another subnetwork (FPCNb) shows negative default coupling-raising questions about how these networks interact during creative cognition. Here we examine frontoparietal subnetwork functional connectivity in a large sample of participants (n = 171) who completed a divergent creative thinking task and a resting-state scan during fMRI. We replicated recent findings on functional connectivity of frontoparietal subnetworks at rest: FPCNa positively correlated with the default network and FPCNb negatively correlated with the default network. Critically, we found that divergent thinking evoked functional connectivity between both frontoparietal subnetworks and the default network, but in different ways. Using community detection, we found that FPCNa regions showed greater coassignment to a default network community. However, FPCNb showed overall stronger functional connectivity with the default network-reflecting a reversal of negative connectivity at rest-and the strength of FPCNb-default network connectivity correlated with individual creative ability. These findings provide novel evidence of a behavioral benefit to the cooperation of typically anticorrelated brain networks., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Relational reasoning is a complex form of human cognition involving the evaluation of relations between mental representations of information. Prior studies have modified stimulus properties of relational reasoning problems and examined differences in difficulty between different problem types. While subsets of these stimulus properties have been addressed in separate studies, there has not been a comprehensive study, to our knowledge, which investigates all of these properties in the same set of stimuli. This investigative gap has resulted in different findings across studies which vary in task design, making it challenging to determine what stimulus properties make relational reasoning-and the putative formation of mental models underlying reasoning-difficult. In this article, we present the Multidimensional Relational Reasoning Task (MRRT), a task which systematically varied an array of stimulus properties within a single set of relational reasoning problems. Using a mixed-effects framework, we demonstrate that reasoning problems containing a greater number of the premises as well as multidimensional relations led to greater task difficulty. The MRRT has been made publicly available for use in future research, along with normative data regarding the relative difficulty of each problem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cortes, Weinberger, Colaizzi, Porter, Dyke, Keaton, Walker and Green.)

A central challenge for creativity research-as for all areas of experimental psychology and cognitive neuroscience-is to establish a mapping between constructs and measures (i.e., identifying a set of tasks that best captures a set of creative abilities). A related challenge is to achieve greater consistency in the measures used by different researchers; inconsistent measurement hinders progress toward shared understanding of cognitive and neural components of creativity. New resources for aggregating neuroimaging data, and the emergence of methods for identifying structure in multivariate data, present the potential for new approaches to address these challenges. Identifying meta-analytic structure (i.e., similarity) in neural activity associated with creativity tasks might help identify subsets of these tasks that best reflect the similarity structure of creativity-relevant constructs. Here, we demonstrated initial proof-of-concept for such an approach. To build a model of similarity between creativity-relevant constructs, we first surveyed creativity researchers. Next, we used NeuroSynth meta-analytic software to generate maps of neural activity robustly associated with tasks intended to measure the same set of creativity-relevant constructs. A representational similarity analysis-based approach identified particular constructs-and particular tasks intended to measure those constructs-that positively or negatively impacted the model fit. This approach points the way to identifying optimal sets of tasks to capture elements of creativity (i.e., dimensions of similarity space among creativity constructs), and has long-term potential to meaningfully advance the ontological development of creativity research with the rapid growth of creativity neuroscience. Because it relies on neuroimaging meta-analysis, this approach has more immediate potential to inform longer-established fields for which more extensive sets of neuroimaging data are already available., (Copyright © 2020. Published by Elsevier Inc.)

Creative thinking drives progress not only in the arts but also, and perhaps especially, in the fields of science, technology, engineering, and mathematics, and it is expected to become even more valuable than technical skill as artificial intelligence outpaces human cognition. Fostering creative thinkers has become a primary focus of educators. Educationally relevant anxieties, like math anxiety, have been shown to substantially impact specific forms of achievement and engagement, both in school and in career pursuits. Identifying these anxieties has led to promising interventions to enable affected individuals to reach their potential. Somewhat surprisingly, however, the possibility of anxiety specific to creative thinking is, to our knowledge, unexplored. In this article, across multiple samples, we tested the viability of creativity anxiety as a construct. We first created a new measure, the Creativity Anxiety Scale (CAS), demonstrating validity, internal reliability, and specificity. Applying the CAS revealed that creativity-specific anxiety predicted individual differences in creative achievement and attitudes toward creativity over and above effects of general anxiety. Moreover, across diverse content domains, from science to arts, anxiety was greater for situations that required creativity than similar situations that did not. Notably, this effect was especially pronounced in women. These findings suggest that creativity anxiety may have wide-reaching impacts and distinguish creativity anxiety from anxiety about noncreative aspects of performance. Establishing creativity anxiety as a novel construct, and the CAS as a valid measurement instrument, opens a new avenue of research that promises to deepen basic understanding of creative cognition and inform development of interventions to enable greater achievement of creative potential. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Synthetic cannabinoids are manufactured clandestinely with little quality control and are distributed as herbal "spice" for smoking or as bulk compound for mixing with a solvent and inhalation via electronic vaporizers. Intoxication with synthetic cannabinoids has been associated with seizure, excited delirium, coma, kidney damage, and other disorders. The chemical alterations produced by heating these structurally novel compounds for consumption are largely unknown. Here, we show that heating synthetic cannabinoids containing tetramethylcyclopropyl-ring substituents produced thermal degradants with pharmacological activity that varied considerably from their parent compounds. Moreover, these degradants were formed under conditions simulating smoking. Some products of combustion retained high affinity at the cannabinoid 1 (CB 1 ) and CB 2 receptors, were more efficacious than (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55,940) in stimulating CB 1 receptor-mediated guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding, and were potent in producing Δ 9 -tetrahydrocannabinol-like effects in laboratory animals, whereas other compounds had low affinity and efficacy and were devoid of cannabimimetic activity. Degradants that retained affinity and efficacy also substituted in drug discrimination tests for the prototypical synthetic cannabinoid 1-pentyl-3-(1-naphthoyl)indole (JWH-018), and are likely to produce psychotropic effects in humans. Hence, it is important to take into consideration the actual chemical exposures that occur during use of synthetic cannabinoid formulations to better comprehend the relationships between dose and effect., (Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.)

Diversion of synthetic cannabinoids for abuse began in the early 2000s. Despite legislation banning compounds currently on the drug market, illicit manufacturers continue to release new compounds for recreational use. This study examined new synthetic cannabinoids, AB-CHMINACA (N-[1-amino-3-methyl-oxobutan-2-yl]-1-[cyclohexylmethyl]-1H-indazole-3-carboxamide), AB-PINACA [N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide], and FUBIMINA [(1-(5-fluoropentyl)-1H-benzo[d]imadazol-2-yl)(naphthalen-1-yl)methanone], with the hypothesis that these compounds, like those before them, would be highly susceptible to abuse. Cannabinoids were examined in vitro for binding and activation of CB1 receptors, and in vivo for pharmacological effects in mice and in Δ(9)-tetrahydrocannabinol (Δ(9)-THC) discrimination. AB-CHMINACA, AB-PINACA, and FUBIMINA bound to and activated CB1 and CB2 receptors, and produced locomotor suppression, antinociception, hypothermia, and catalepsy. Furthermore, these compounds, along with JWH-018 [1-pentyl-3-(1-naphthoyl)indole], CP47,497 [rel-5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol], and WIN55,212-2 ([(3R)-2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone, monomethanesulfonate), substituted for Δ(9)-THC in Δ(9)-THC discrimination. Rank order of potency correlated with CB1 receptor-binding affinity, and all three compounds were full agonists in [(35)S]GTPγS binding, as compared with the partial agonist Δ(9)-THC. Indeed, AB-CHMINACA and AB-PINACA exhibited higher efficacy than most known full agonists of the CB1 receptor. Preliminary analysis of urinary metabolites of the compounds revealed the expected hydroxylation. AB-PINACA and AB-CHMINACA are of potential interest as research tools due to their unique chemical structures and high CB1 receptor efficacies. Further studies on these chemicals are likely to include research on understanding cannabinoid receptors and other components of the endocannabinoid system that underlie the abuse of synthetic cannabinoids., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

Synthetic indole-derived cannabinoids, originally developed to probe cannabinoid CB1 and CB2 receptors, have become widely abused for their marijuana-like intoxicating properties. The present study examined the effects of indole-derived cannabinoids in rats trained to discriminate Δ(9)-tetrahydrocannabinol (Δ(9)-THC) from vehicle. In addition, the effects of Δ(9)-THC in rats trained to discriminate JWH-018 from vehicle were assessed. Adult male Sprague-Dawley rats were trained to discriminate 3mg/kg Δ(9)-THC or 0.3mg/kg JWH-018 from vehicle. JWH-018, JWH-073, and JWH-210 fully substituted in Δ(9)-THC-trained rats and Δ(9)-THC substituted in JWH-018-trained rats. In contrast, JWH-320, an indole-derived cannabinoid without affinity for CB1 receptors, failed to substitute for Δ(9)-THC. Pre-treatment with 1mg/kg rimonabant significantly reduced responding on the JWH-018-associated lever in JWH-018-trained rats. These results support the conclusion that the interoceptive effects of Δ(9)-THC and synthetic indole-derived cannabinoids show a large degree of overlap, which is predictive of their use for their marijuana-like intoxicating properties. Characterization of the extent of pharmacological differences among structural classes of cannabinoids, and determination of their mechanisms remain important goals., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Risk stratification of patients with acute upper GI bleeding (UGIB) in the emergency room (ER) enables appropriate triage to urgent endoscopy and therapeutic intervention., Aim: The aim of this study was to evaluate the ability of Live View Video Capsule Endoscopy (VCE) with Pillcam Eso(®) to accurately identify high and low risk patients with UGIB., Methods: Twenty-four patients with a history of UGIB within 48 h of admission to the ER were randomized to VCE versus standard clinical assessment. VCE was read real-time at the bedside and later reviewed after download. Positive VCE findings included coffee grounds, blood clot, red blood, or a bleeding lesion. VCE positive patients underwent EGD within 6 h. Control patients and VCE negative patients underwent EGD within 24 h., Results: Seven of 12 patients were VCE positive. All seven had confirmatory stigmata at EGD. Of the five VCE negative patients, four had no stigmata at EGD and one was not endoscoped due to comorbidities. The actual lesion was visualized at VCE in four of 12 patients during live view and in an additional two patients after download (6/12). Time to endoscopy in the VCE positive group was significantly shorter than control patients (2.5 vs. 8.9 h, P = 0.029). There was no mortality. Blood transfusion requirement and length of stay were not significantly different in the two groups., Conclusions: Live view VCE accurately identifies high and low risk ER patients with UGIB. Use of VCE to risk stratify these patients significantly reduced time to emergent EGD and therapeutic intervention.

Objective: To evaluate the ability of a tumor-head volume ratio to predict outcome and incidence of hydrops in fetuses with sacrococcygeal teratoma., Methods: Seventy-one sonograms were reviewed retrospectively from 28 fetuses with sacrococcygeal teratoma managed in our institution. Head volume (HV) and total tumor volume were calculated from sonograms. Amount of cystic tumor was estimated to determine solid tumor volume (STV) for the STV/HV ratio., Results: Twenty percent of sonograms with STV/HV <1 and 97.3% with STV/HV >1 were associated with 1 or more abnormal sonographic signs (p = 0.000). Overall mortality was 11/27 (41%). There was no mortality in fetuses with a ratio of <1, while 11/18 (61%) of fetuses with ratio >1 died (p = 0.003)., Conclusion: The STV/HV ratio may be used to identify fetuses with a high risk of a poor outcome due to high-output cardiac failure and hydrops, and may help guide management.

Background: Rectovaginal fistula (RVF) is an abnormal epithelium-lined communication between the wall of the rectum and the posterior vaginal wall. The incidence of RVFs is low and accounts for about 5% of all anorectal fistulas. Women who suffer from an RVF complain of uncontrollable passage of gas or feces from the vagina. This remains a major contributor to morbidity associated with this condition in terms of social, psychologic, and sexual dysfunction., Objective: RVFs may be managed both medically and surgically, with the latter being the preferred option. A number of different surgical techniques that pertain to fistula closure were described in various literature; however, very little has been said of much-less-invasive techniques and alternatives to surgical correction if the patient is a poor candidate or prefers not to have surgery. The purpose of our article is to show our approach in treating an RVF, given the fact that our patient was a poor surgical candidate and, moreover, refused more-invasive techniques for treatment., Design: A case report. The patient described in this article is a 77-year-old woman with comorbidities that limited her as a candidate for less-invasive techniques rather than surgery., Setting: An inpatient at New York Hospital Queens, Flushing, New York., Patient: A 77-year-old woman, with a medical history of 2 myocardial infarctions, congestive heart failure, 2 cardiac stents, multiple urinary-tract infections, and diverticulitis, presented to the hospital with a fever of 38.3 degrees C (101 degrees F) for 2 days. On the second day of admission, the patient complained of passing stool and flatus from the vagina. A subsequent workup and sigmoidoscopy revealed an RVF., Intervention: A sigmoidoscopy was performed, and fistula closure was achieved in 2 phases with the use of a Resolution clip., Main Outcome Measurements: Complications and resolution of symptoms after the procedure were the primary end points., Results: No complications were noted post procedure, and the patient has remained free of any complaints now for 12 months., Limitations: The main limitation of the study is that this is a case report limited to a single patient, and outcomes of the procedure were concluded based on this particular patient. The endoscopic technique described here may be limited to readily visualized fistulas at endoscopy that are amenable to this treatment option., Conclusions: The technique described, closing an RVF with the use of an endoscopically placed Resolution clip, shows great promise and could be applied to treating uncomplicated fistulas.

Undetectable hepatitis C virus (HCV) RNA [RNA(-)] before liver transplantation (OLT) has been shown to decrease the rates of disease recurrence. We sought to determine whether RNA(-) subjects differ in post-OLT recurrence (virological/VR, histological/HR), graft failure (GF), or patient survival from RNA(+) patients using a retrospective review. From 1995 to 2004, a total of 49 patients were RNA(-) at OLT as a result of interferon-based therapy: 22 SVR and 27 with end-of-treatment response (ETR) transplanted when RNA(-) within 6 months of ET. Forty-eight RNA(+) patients were analyzed as controls. Virological recurrence (VR) was seen in 55% of RNA(-) subjects with no difference in HR between RNA(-) vs (+) groups, namely 36.7% versus 56.3% (P = .068), respectively. The RNA(+) subjects showed a lower time to HR (5.6 vs 11 months; P = .027). The SVR subjects displayed lower VR (36.4%) and histological recurrence (HR) (13.6%) compared to ETR (VR 70.4%, P = .023; HR 55.6%, P = .003) or RNA(+) (HR 56%, P = .0008). The SVR subjects, who were identified with a sensitive assay (SVR(S), lower limit <600 IU/mL) showed no VR, HR, or GF. The 1- and 5-year survivals were 87.8%/75.6% and 89.6%/77.8% for RNA(-) and (+) groups, respectively (P = .77). In conclusion, RNA(-)-transplanted patients displayed lower VR and longer time to HR. The SVR patients showed lower VR and HR compared to ETR and RNA(+) patients.

Background/purpose: Surgical intervention that improves pancreatic ductal drainage is a reasonable treatment strategy for recurrent pancreatitis in children., Methods: This study was approved by the Committee on Human Research (San Francisco, CA). A retrospective chart review was performed on children aged 0 to 17 years given the International Classification of Diseases, Ninth Revision coding diagnosis of chronic pancreatitis who underwent surgical intervention from 1981 to 2005., Results: From 1981 to 2005, 32 children were treated for the diagnosis of chronic pancreatitis. The etiologies were obstructive (n = 13), idiopathic (n = 10), hereditary (n = 6), medications (n = 2), and infection (n = 1). Fifteen patients underwent 17 operations for chronic pancreatitis, including Puestow (n = 9), cystenterostomy (n = 2), Whipple (n = 1), distal pancreatectomy (n = 1), Frey (n = 1), DuVal (n = 1), excision of enteric duplication cyst (n = 1), and pancreatic ductal dilation (n = 1). The mean age at presentation of patients undergoing surgery was 6.0 +/- 4.1 years (mean +/- SD). The mean time from presentation to operation was 3.3 +/- 3.3 years. There were no deaths after surgical intervention. Of 15 patients, 2 (13%) required rehospitalization within 90 days of surgery, one for bowel obstruction, the other for splenic infarction. The median length of stay postoperatively was 8 days (range, 5-66 days)., Conclusions: Chronic pancreatitis in children differs markedly in etiology when compared with adults. In most cases seen in our institution, chronic pancreatitis resulted from ineffective ductal drainage. These disorders are amenable to surgical decompression, which, ultimately, can prevent disease recurrence.

Serum markers of liver fibrosis are difficult to validate, due to the sampling error and observer variability associated with percutaneous liver biopsies. Laparoscopic biopsy decreases sampling error and increases the reliability of histopathologic assessment. We prospectively evaluated the FIBROSpect(SM) II serum marker test for viral liver fibrosis against laparoscopic biopsies by studying 145 patients with chronic hepatitis B or C who underwent laparoscopy in a tertiary care setting. Serum samples obtained at biopsy were tested with FIBROSpect II to assess the degree of fibrosis. Multiple biopsies were obtained from each patient and scored blindly using the Batts-Ludwig system. An average biopsy stage was calculated and the performance of the test panel assessed. FIBROSpect II was able to rule in significant fibrosis (stages 2-4), with a likelihood ratio of 2.6. It correctly indicated absence of disease in 74% of stages 0-1 patients and correctly predicted significant disease in 67% of stages 2-4 patients. Test correlation was highest with Batts-Ludwig stages 3 (77%) and 4 (96%) and lowest with stage 2 (43%). Multiple biopsies from 52% of patients differed by at least 1 stage. In 13 patients (9%), cirrhosis was detected by laparoscopy but not histologically; in 4 (3%), a stage of 4 was obtained, but cirrhosis was not evident by laparoscopy. FIBROSpect II provided valuable additional information for assessing fibrosis. The discordance in fibrosis stage seen in multiple biopsies from the same patient underscores the need to consider all available information when assessing fibrosis. This study confirms and extends results of previous studies evaluating FIBROSpect II using percutaneous liver biopsy.

Purpose: The natural history of certain prenatally diagnosed masses is well known. Large thoracic mass lesions can evolve one of 2 ways, either to regress and cause minimal morbidity, or to progress and enlarge, often resulting in hydropic changes in the fetus. This nonimmune hydrops carries a dismal prognosis, with nearly all fetuses expiring before or shortly after birth. However, hydrops associated with fetal mass lesions can be halted and even reversed with fetal intervention and treatment of the underlying defect. We examined our patients with fetal mass lesions to evaluate survival after intervention., Methods: Institutional approval was obtained by the Committee on Human Research. A retrospective review was performed of 294 fetuses evaluated over 15 years with large mass lesions. All patients were evaluated for evidence of fetal hydrops using ultrasound criteria. Patients were divided according to type of intervention. Primary outcome measure was 30-day survival after birth., Results: (1) Patients without fetal hydrops did not undergo fetal intervention and survived to 30 days after birth (167/172, 97%). (2) Patients with fetal mass lesions that developed hydrops fared poorly with no intervention (1/33 survival, 3%), whereas fetuses undergoing prenatal intervention fared much better (15/30 open, 50%; 3/10 percutaneous, 30%). (3) Four patients with hydropic congenital cystic adenomatoid malformation (n = 3) or pulmonary sequestration (n = 1) received steroids in preparation for surgery but underwent no intervention, and the patients survived the neonatal period., Conclusion: Fetuses with prenatal diagnoses of masses not associated with hydrops have excellent prognosis with survival higher than 95%. Nonimmune hydrops associated with prenatal diagnosis of a fetal mass is a devastating complication with less than 5% survival. Open resection of a mass causing hydrops resulted in 50% survival, with reversal of hydrops in a group with near-uniform fatality. Further investigation is warranted regarding the use of minimally invasive prenatal therapies including steroid administration for hydropic fetuses.

Purpose: The sequelae of congenital diaphragmatic hernia (CDH) continue well beyond the perinatal period. Up to 50% of these patients have subsequent recurrent herniation or small bowel obstruction (SBO). A recent trend has been toward the use of bioactive prosthetic materials. We reviewed different patch closure techniques used for CDH repair at our institution and their association with these sequelae., Methods: A retrospective review was performed of 152 records for patients with CDH. Newborns that underwent patch repair for CDH and survived for at least 30 days were included in the analysis. Primary outcomes evaluated were recurrent herniation and SBO. Two types of prostheses were examined, Gore-Tex, an artificial material, and Surgisis, a bioactive material., Results: Twelve (44%) of 27 patients who had Surgisis repair had recurrent herniation. Seventeen (38%) of 45 patients who had a Gore-Tex repair had recurrent herniation. Two additional patients in each group presented with SBO. No significant difference in recurrent herniation rates was observed (P > .5). The time to recurrence was similar in both groups (log-rank, P = .75), with most recurrences (92% Surgisis, 76% Gore-Tex) occurring in the first year., Conclusion: The rates of recurrent herniation and SBO after neonatal prosthetic patch repair of CDH were similar regardless of the prosthetic material used (Surgisis or Gore-Tex).

Purpose: The aim of this study was to determine if patients are in remission or weaning off medication after thymectomy for myasthenia gravis (MG) and to examine the thoracoscopic versus open approaches., Methods: A retrospective review of all patients who underwent thymectomy for MG at a tertiary referral center between 1992 and 2004 (N = 14). Six patients (42.9%) underwent thoracoscopic resection. Eight patients underwent open resection; 5 (35.7%) had median sternotomy and 3 (21.4%) by transcervical approaches. Follow-up was obtained in 12 (85.7%) of 14 patients by both chart review and telephone. The mean follow-up was 43.0 months (range, 4-111 months). Statistical significance was determined by Student's t test or Fisher's Exact Test., Results: The thoracoscopic group had a mean operating time of 138.8 minutes compared with 139.8 minutes in the open group (P = .9). The thoracoscopic group had a mean estimated blood loss of 7.5 mL compared with 52.5 mL in the open group (P = .02). The mean length of stay for the thoracoscopic group was 1.5 days (range, 1-2 days) and was 10.6 days (range, 3-41 days) in the open group (P = .13). Three (60%) of 5 patients were entirely off medication in the thoracoscopic group at the time of follow-up compared with 3 (50%) of 6 patients in the open group (P = 1.0). In the thoracoscopic group, 5 (83.3%) of 6 were in class 1 to 3 of the DeFilippi classification (complete remission or improved with decreased medication requirements). One patient had no change in symptoms (class 4). In the open group, 5 (83.3%) of 6 were classified as DeFilippi 1 to 3 at the time of follow-up, and one patient had worsening symptoms (class 5)., Conclusions: Both thoracoscopic and open approaches to thymectomy in patients with MG are effective, with more than 80% of patients in both groups in remission or with improvement at the time of follow-up. The thoracoscopic group has the added benefits of decreased estimated blood loss, decreased length of hospital stay, and improved cosmesis. We advocate the thoracoscopic approach for thymectomy in the treatment of juvenile MG.

Objective: Amniotic access for fetal diagnosis and therapy can lead to membrane leaks, separation, and preterm premature rupture of membranes. Morbidity limits the beneficial effects of fetal intervention. We propose to examine a novel preventive "presealant" membrane puncture technique and evaluate it in vitro., Study Design: Fetal membranes from normal term deliveries were fastened to a pressure controlled pump and punctured after presealant placement. Distinct bioadhesives were then compared for sealing efficacy by the measurement of leak pressures. Membranes were also evaluated for changes in tensile rupture strength after treatment., Results: Preemptive sealing by 2 of the presealants achieved significantly higher leak pressures compared with control membranes (85 and 78, respectively, vs 27 cm of water; P < .05). One of the presealants worked effectively in a membrane-sealant-membrane interface (62 vs 30 cm of water; P < .05). All treated membranes, however, demonstrated diminished tensile rupture forces compared with control membranes (124 vs 170 g/cm2; P > .05)., Conclusion: The application of a presealant is effective for the prevention of iatrogenic rupture in an in vitro model and may be beneficial for clinical application. Further studies with different bioadhesives are needed, given the limitations of the glues that are described in this study.

Hepatitis B virus (HBV) infection is an ongoing worldwide pandemic. In general, the mode of transmission is different according to its prevalence in different areas: mostly perinatal in highly prevalent zones and predominantly sexual and/or parenteral in low prevalence areas. The variation in presentations of chronic hepatitis B (CHB) make its management complex. Aminotransferase levels, viral load, histologic changes, age of the patient, viral mutations (e.g. hepatitis B e antigen negative) and pregnancy are all factors that impact on treatment decisions. The ideal drug that will eradicate the HBV has yet to be developed. This review focuses on the currently available medications for CHB: alpha-interferon, lamivudine, adefovir, as well as new drugs that have proven to be active against HBV in clinical trials and are closer to licensure; pegylated interferon tenofovir, entecavir, emtricitabine, telbivudine and clevudine. The antiviral properties and the advantages and disadvantages in HBeAg-positive and negative patients are discussed. Combinations of different medications currently under study were not included in this review. A suggested algorithm, developed from recent literature, may serve as a practical guide on tailoring drug selection based on viral load, aminotransferases, hepatitis B e antigen status and histological findings. Finally, practical management questions are raised.

Background/purpose: Fetal tracheal occlusion (TO) was developed in an attempt to enhance prenatal lung growth and improve survival in fetuses with severe congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled clinical trial in 24 fetuses with severe left CDH (liver herniated into the thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO vs standard perinatal care (control) and prospectively followed up the 16 survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical, growth, and nutritional outcomes., Methods: At 1 and 2 years old, subjects underwent evaluation consisting of medical and neurological history and physical, developmental testing, nutritional assessment, oxygen saturation and pulmonary function testing, chest radiograph, and echocardiogram. Growth and developmental measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank sum test, Fisher's Exact test, and logistic and linear regression., Results: Infants with TO were significantly more premature at birth (control vs TO, 37.4 +/- 1.0 vs 31.1 +/- 1.7 weeks; P < .01). Growth failure ( z score for weight <2 SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs 86%; P = .31). There was considerable catch-up growth by age 2 years (growth failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other growth parameters. There were also no differences in neurodevelopmental outcome at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P = .02, respectively). Hearing loss requiring amplification has been diagnosed in 44% of the group (control vs TO, 44% vs 43%; P = 1.0)., Conclusions: In this group of infants with severe CDH, there were no differences in outcome at 2 years old despite significant prematurity in the TO group. Oxygen supplementation at hospital discharge identified the most vulnerable group with respect to neurodevelopmental outcome, but all infants had significant growth failure, and hearing impairment is a substantial problem in this population. Severe CDH carries significant risk of chronic morbidity.

Fetal surgery is now an accepted modality for treatment of a variety of lethal and non-lethal congenital conditions. It represents a new, fast-moving frontier of medicine in which cooperative mulitdisciplinary effort and input are required to assure both fetal and maternal welfare. A wide range of therapeutic strategies from percutaneous to open invasive techniques has led to a complex list of different procedures for different diseases. This review identifies the most common disease entities managed by fetal intervention, examines the evolution in development of techniques to those currently used, and describes the prospective, randomized trials presently underway that are designed to establish the safety and determine true efficacy of treatment. Fetal surgery as a (multi)discipline continues to strive to minimize maternal and fetal risk. Undoubtedly, as tocolytic therapy and neonatal intensive efforts improve, fetal therapy will expand.