Search

The confrontation of prejudicial acts and comments promotes multiple benefits, most notably the prevention of future prejudicial remarks and the reduction of stereotype use. Research, however, consistently shows low rates of confronting prejudice, particularly regarding sexism. Here, we examine whether personal sense of power, known to increase action and activate the behavioral approach system, increases the likelihood of confronting a sexist remark. In Study 1, we demonstrate that for both women and men, self-reported power is associated with a higher frequency of confronting sexism. In Study 2, we manipulate women's sense of power (i.e., high power, low power, or control) and subsequently present an opportunity to confront a sexist remark. Results show that women primed to feel powerful were more likely to confront the sexist remark and expressed greater disagreement with the comment, compared to women primed to feel powerless. Implications for the confronting literature and behavior are discussed.

In recent years, a variety of emerging online media, such as TikTok, Kuaishou, YouTube and other short video application platforms, have appeared. The problem of short video addiction has become an issue to education experts and the general public, as students' excessive use of short video has become increasingly serious with many hidden concerns to the students' learning effectiveness. In addition, to meet the growing demand for innovative design talents worldwide, the Taiwan government has been committed to promoting policies related to the cultivation of innovative and creative talents nowadays, particularly for innovative design profession students who often use the Internet and short videos for learning. Therefore, the study aims to use questionnaires to understand the habits and addiction of the innovative design profession students in using short videos, and to further investigate the relation of short video addiction to the students' creative self-efficacy (CSE) and career interests. A total of 561 valid questionnaires were collected after eliminating invalid questionnaires and reliability analysis. Structural equation modeling and model validation were conducted afterwards. The results showed that short video addiction had a negative effect on CSE; CSE had a positive effect on career interests; and CSE had an indirect effect between short video addiction and career interests.

Background: The Patient Autonomy Act was implemented in Taiwan on 6 January 2019. It is the first patient-oriented act in Taiwan, and also the first special act to completely protect patient autonomy in Asia. Our study aimed to investigate the web resources citizens were able to access on the eve of the implementation of the Patient Autonomy Act in Taiwan., Methods: Patient Autonomy Act-related web resources were searched for by entering 10 related terms individually into the Google search engine in January 2019 and again in April 2019. Search activity data were analyzed using Google Trends., Results: "Advance care planning" and "advance decision" were the most relevant keywords for finding information about the Patient Autonomy Act on the eve of the act's implementation in Taiwan. The main online information sources were non-governmental websites including news sites and online magazines. The related search volume only increased on the eve of implementation., Conclusions: Even though the Patient Autonomy Act was first published three years before its implementation, the related search volume only increased on the eve of its implementation. Therefore, whether the three-year buffer between its publication and implementation was necessary requires further investigation.

Although echocardiography is usually diagnostic of cardiac tamponade, it may not be readily available at the point-of-care. We sought to develop and validate a measurement of respirophasic variation in the amplitude of pulse oximetry plethysmographic waveforms as a diagnostic tool for cardiac tamponade. Pulse oximetry plethysmographic waveforms were recorded, and the ratio of maximum-to-minimum measured amplitude of these waveforms from one respiratory cycle was calculated by blinded observers. Ratios from 3 consecutive respiratory cycles were then averaged to derive an "oximetry paradoxus" ratio. Cardiac tamponade was independently confirmed or excluded according to a "blinded" objective interpretation of echocardiography or right heart catheterization. Seventy four subjects were enrolled (51% men; mean age 54 ± 15 years); 19 of whom had cardiac tamponade. Oximetry paradoxus area under the curve for diagnosis of cardiac tamponade was 0.90 (95% confidence interval, 0.84 to 0.97); its diagnostic performance was superior to sphygmomanometer-measured pulsus paradoxus (area under the curve difference = 0.16, p = 0.022). In a derivation cohort (n = 37; tamponade, 9 cases), 3 diagnostic oximetry paradoxus thresholds were identified and validated in an independent validation cohort (n = 37; tamponade, 10 cases): 1.2 (100% sensitivity, 44% specificity), 1.5 (80% sensitivity, 81% specificity), and 1.7 (80% sensitivity, 89% specificity). Furthermore, oximetry paradoxus was significantly reduced after draining pericardial fluid. In conclusion, we defined and validated oximetry paradoxus as a simple and ubiquitous point-of-care test to diagnose cardiac tamponade using respirophasic changes in pulse plethysmography waveforms. This test can aid in identifying patients with cardiac tamponade, thus expediting confirmatory testing and life-saving treatment., (Copyright © 2018. Published by Elsevier Inc.)

Background: In the Internet era, many web-based appointment systems for hospitals have been established to replace traditional systems. Our study aimed to highlight the features of online appointment systems for hospitals in Taiwan, where patients can visit outpatient departments without a referral., Methods: All hospitals online appointment systems were surveyed in October 2018. Features of first-visit registrations were analyzed and stratified according to the hospitals' accreditation levels., Results: Of the 417 hospitals, 59.7% (249) had public online appointment systems. For first-visit patients, only 199 hospitals offered the option of making appointments online from 7 to 98 (mean 38.9) days prior to the appointment itself. Before appointments, 68 (34.2%) hospitals recommended specialties for patients to choose according to their symptoms, and only 11 (5.5%) had a function for sending messages to doctors. After appointments, 176 (88.4%) provided links to real-time monitoring of outpatient service progress., Conclusions: More than half of the hospitals in Taiwan have public online appointment systems. However, most of these systems simply fulfill the function of registration, and rarely take the opportunity to improve efficiency by gathering information regarding patients' medical history or reasons for making the appointment.

A real-time cost and power-efficient (CPE) set partitioning in hierarchical trees (SPIHT) decoder design with low hardware complexity and low-power dissipation is introduced in one-dimension (1-D) wavelet-based quality-assured electrocardiograph (ECG) compression systems for mobile health (mHealth) applications. However, current SPIHT coding architectures are designed for image/video processing. These architectures require a large amount of memory as well as complicated sorting algorithms, which both require time-consuming tasks and are unsuitable for mobile ECG applications. Based on our previously modified SPIHT coding work, which used flags and check bits to reduce memory requirements and coding complexity by merging three search processes into one step. Therefore, to achieve the real-time design goal for mobile ECG applications, in this paper, we first introduce a hardware-oriented SPIHT decoding algorithm that is suitable for decoding the previously presented SPIHT coding work. Accordingly, an appropriate low-power hardware architecture is developed to implement a real-time high-performance and low-cost SPIHT VLSI design for our proposed decoder algorithm, which is appropriate for mobile ECG applications. Using the distinct ECG signals in the MIT-BIH arrhythmia database (sampling rate of 360 Hz), the final simulation and VLSI implementation results reveal that the proposed CPE SPIHT decoder design outperforms the state-of-the-art designs in terms of the average decoding time, the decoding quality, the VLSI speed, and the power consumption. Most importantly, the design can be exploited to a 1-D 1024 × 1 wavelet-based quality-assured ECG data compression system.

In this paper, a speed and power-efficient set partitioning in hierarchical trees (SPIHT) design is introduced for one-dimensional (1-D) wavelet-based electrocardiography (ECG) compression systems with quality guarantee. To achieve real-time and low-power design objectives toward wearable quality-on-demand (QoD) ECG applications, we first propose a coding-time- and computation-efficient SPIHT algorithm using various types of coding status register files to overcome the disadvantages of low coding speeds and complicated hardware architectures characterizing prior SPIHT algorithms resulting from the necessity of dynamic computation and arrangement in the sorting and refinement processing phase. Second, a highly pipelined and power-efficient very large scale integration (VLSI) architecture is developed to implement a high-performance and low-power SPIHT design based on the proposed algorithm. The final simulation results demonstrate that our proposed algorithm can speed up the average coding time 1.52 to 2.74 times compared to prior work with an identical compression ratio for an 11-level $1024\times 1\,1-{\rm{D}}$ discrete wavelet transform at diverse target percentage root-mean-square differences (PRDT) on various MIT-BIH arrhythmia datasets. Applied to wearable wavelet-based QoD ECG applications, our proposed VLSI architecture attains a working frequency of 740 MHz and consumes an average of $\text{23}\ \mu {\text{W}}$ of power with Taiwan Semiconductor Manufacturing Company 90-nm CMOS technology, which shows the effectiveness of speed and power over the state-of-the-art designs.

Background : Social media advertising has become increasingly influential in recent years. Because Facebook has the most active users worldwide, many hospitals in Taiwan have created official Facebook fan pages. Our study was to present an overview of official Facebook fan pages of hospitals in Taiwan. Methods : All 417 hospitals were surveyed about their use of Facebook fan pages in December 2017. The last update time, posts in the past 30 days, number of “Likes”, and other features were analyzed and stratified according to the accreditation statuses of the hospitals. Results : In Taiwan, only 51.1% ( n = 213) of the hospitals had an official Facebook fan page. Among these hospitals, 71.8% ( n = 153) had updated their pages in the past 30 days, although 89.2% ( n = 190) provided online interactions. Academic medical centers tended to have more “Likes” than regional and local community hospitals (on average 5947.4, 2644.8, and 1548.0, respectively). Conclusions : In spite of the popularity of Facebook among the general population, most hospitals in Taiwan do not seem to make good use of this kind of social media. The reasons for the use and nonuse of Facebook on the part of both hospitals and patients deserve further investigation.

Background: Aberrant hypermethylation of cellular genes is a common phenomenon to inactivate genes and promote tumorigenesis in nasopharyngeal carcinoma (NPC)., Methods: Methyl binding domain (MBD)-ChIP sequencing of NPC cells, microarray data of NPC biopsies and gene ontology analysis were conducted to identify a potential tumor suppressor gene CLDN11 that was both hypermethylated and downregulated in NPC. Bisulfite sequencing, qRT-PCR, immunohistochemistry staining of the NPC clinical samples and addition of methylation inhibitor, 5'azacytidine, in NPC cells were performed to verify the correlation between DNA hypermethylation and expression of CLDN11. Promoter reporter and EMSA assays were used to dissect the DNA region responsible for transcription activator binding and to confirm whether DNA methylation could affect activator's binding, respectively. CLDN11 was transiently overexpressed in NPC cells followed by cell proliferation, migration, invasion assays to characterize its biological roles. Co-immunoprecipitation experiments and proteomic approach were carried out to identify novel interacting protein(s) and the binding domain of CLDN11. Anti-tumor activity of the CLDN11 was elucidated by in vitro functional assay., Results: A tight junction gene, CLDN11, was identified as differentially hypermethylated gene in NPC. High methylation percentage of CLDN11 promoter in paired NPC clinical samples was correlated with low mRNA expression level. Immunohistochemistry staining of NPC paired samples tissue array demonstrated that CLDN11 protein expression was relatively low in NPC tumors. Transcription activator GATA1 bound to CLDN11 promoter region - 62 to - 53 and its DNA binding activity was inhibited by DNA methylation. Re-expression of CLDN11 reduced cell migration and invasion abilities in NPC cells. By co-immunoprecipitation and liquid chromatography-tandem mass spectrometry LC-MS/MS, tubulin alpha-1b (TUBA1B) and beta-3 (TUBB3), were identified as the novel CLDN11-interacting proteins. CLDN11 interacted with these two tubulins through its intracellular loop and C-terminus. Furthermore, these domains were required for CLDN11-mediated cell migration inhibition. Treatment with a tubulin polymerization inhibitor, nocodazole, blocked NPC cell migration., Conclusions: CLDN11 is a hypermethylated and downregulated gene in NPC. Through interacting with microtubules TUBA1B and TUBB3, CLDN11 blocks the polymerization of tubulins and cell migration activity. Thus, CLDN11 functions as a potential tumor suppressor gene and silencing of CLDN11 by DNA hypermethylation promotes NPC progression.

Background/purpose: Anterior crossbite correction is common in orthodontic treatment; however, few studies have discussed the change with cephalometric measurements. The purpose of this study was to evaluate the dentofacial changes in anterior crossbite correction by using an upper lingual arch with finger springs., Materials and Methods: This retrospective study included 30 patients (13 female and 17 male). According to the number of crossbite teeth, the patients were divided into three groups. We used paired t test, Kruskal-Wallis test, Mann-Whitney U test, and multiple regression analysis to perform statistical analysis., Results: According to overall treatment changes, the dental changes included overjet increase, overbite decrease, upper incisor proclination, lower incisor retroclination and intrusion, upper molar distal tipping with extrusion, and lower molar intrusion. These dental changes resulted in clockwise mandibular rotation and lip position change. Anterior crossbite correction did not require increasing bite appliances. According to multiple regression analysis, the change in overjet was associated with the position of the upper and lower incisor crown tips. The mean rate of upper incisor movement in the horizontal direction was 2.5 mm/mo. The treatment duration exhibited no significant difference among the three groups., Conclusion: Lingual arch with finger springs was effective in anterior crossbite correction regardless of the number of crossbite teeth.

Objectives: To reevaluate risk factors for high defibrillation threshold (DFT) and propose a risk assessment tool., Background: Controversy exists over routine DFT testing during implantable cardioverter defibrillator (ICD) placement., Methods: We retrospectively analyzed 1,642 consecutive patients who received an ICD and underwent DFT testing., Results: The incidence of high DFT requiring addition of a subcutaneous array was 2.3%. Five significant independent variables predictive of high DFT were identified, including younger age, male gender (hazard ratio 1.99), left ventricular (LV) dysfunction, secondary prevention (hazard ratio 2.33), and amiodarone use (hazard ratio 2.39). Each 10-year increase in age was indicative of a 0.35-times lower chance of high DFT. Each 10% increase of LV ejection fraction (EF) was indicative of a 0.52-times lower chance of high DFT. These five variables form the EF-SAGA risk score (LVEF < 20%, Secondary prevention ICD indication, Age < 60 years, male Gender, Amiodarone use). Cumulative risk of high DFT increased incrementally; patients with four or more variables had an 8.9% likelihood of high DFT. Importantly, primary prevention patients with LVEF > 20% had a negative predictive value for high DFT of 99.3%., Conclusion: We identified five independent predictors of high DFT. We propose the EF-SAGA risk score to help decision making. Primary prevention patients with an LVEF > 20% had an exceedingly low incidence of high DFT suggesting that testing could be avoided in these patients. Careful assessment of the risk-benefit ratio of testing is important in high-risk patients., (©2016 Wiley Periodicals, Inc.)

Background: The Mesopsychidae is an extinct family of Mecoptera, comprising eleven described genera from Upper Permian to Lower Cretaceous deposits. In 2009, several well-preserved mesopsychids with long proboscides were reported from the mid Mesozoic of Northeastern China, suggesting the presence of pollination mutualisms with gymnosperm plants and highlighting their elevated genus-level diversity. Since that time, additional mesopsychid taxa have been described. However, the phylogeny of genera within Mesopsychidae has not been studied formally, attributable to the limited number of well-preserved fossils., Results: Here, we describe two new species, Lichnomesopsyche prochorista sp. nov. and Vitimopsyche pristina sp. nov. and revise the diagnosis of Lichnomesopsyche daohugouensis Ren, Labandeira and Shih, 2010, based on ten specimens from the latest Middle Jurassic Jiulongshan Formation of Inner Mongolia, China. After compiling data from these new fossil species and previously reported representative taxa, we conducted phylogenetic analyses and geometric morphometric studies that now shed light on the taxonomy and phylogeny of Mesopsychidae. We also evaluate the recurring origin of the siphonate proboscis in the Mecoptera and propose an evolutionary developmental model for its multiple origins., Conclusions: Phylogenetic and geometric morphometric results confirm the establishment of two new species, each to Lichnomesopsyche and Vitimopsyche. Vitimopsyche pristina sp. nov. extends the existence of the genus Vitimopsyche Novokshonov and Sukacheva, 2001, from the mid Lower Cretaceous to the latest Middle Jurassic. Two methods of analyses indicate an affiliation of Mesopsyche dobrokhotovae Novokshonov, 1997 with Permopsyche Bashkuev, 2011. A phylogenetic analysis of the Mesopsychidae supports: 1), Mesopsychidae as a monophyletic group; 2), Mesopsyche as a paraphyletic group, to be revised pending future examination of additional material; and 3), the independent origin of the proboscis in the Pseudopolycentropodidae, its subsequent loss in earliest Mesopsychidae such as Epicharmesopsyche, its re-origination in the common ancestor (or perhaps independently) in the Vitimopsyche and Lichnomesopsyche clades of the Mesopsychidae. The third conclusion indicates that the proboscis originated four or five times within early Mecoptera, whose origin is explained by an evolutionary developmental model.

Background: The quantification of tumor heterogeneity with molecular images, by analyzing the local or global variation in the spatial arrangements of pixel intensity with texture analysis, possesses a great clinical potential for treatment planning and prognosis. To address the lack of available software for computing the tumor heterogeneity on the public domain, we develop a software package, namely, Chang-Gung Image Texture Analysis (CGITA) toolbox, and provide it to the research community as a free, open-source project., Methods: With a user-friendly graphical interface, CGITA provides users with an easy way to compute more than seventy heterogeneity indices. To test and demonstrate the usefulness of CGITA, we used a small cohort of eighteen locally advanced oral cavity (ORC) cancer patients treated with definitive radiotherapies., Results: In our case study of ORC data, we found that more than ten of the current implemented heterogeneity indices outperformed SUVmean for outcome prediction in the ROC analysis with a higher area under curve (AUC). Heterogeneity indices provide a better area under the curve up to 0.9 than the SUVmean and TLG (0.6 and 0.52, resp.)., Conclusions: CGITA is a free and open-source software package to quantify tumor heterogeneity from molecular images. CGITA is available for free for academic use at http://code.google.com/p/cgita.

Coronary artery disease (CAD) is a major cause of systolic heart failure (HF). Identifying CAD as a cause of systolic HF has prognostic and treatment implications. Whether all patients with systolic HF of unclear etiology should undergo coronary angiography has been controversial. We sought to derive and validate a clinical prediction rule to exclude CAD as a cause of systolic HF. A derivation cohort was formed of consecutive patients who had undergone coronary angiography with a primary diagnosis of systolic HF of unclear etiology (ejection fraction <50%). Using multivariate logistic regression analysis, we derived a prediction rule for severe CAD (≥50% diameter stenosis in the left main, 3-vessel CAD, and 2-vessel CAD involving the proximal left anterior descending artery). The diagnostic performance of the defined prediction rule was prospectively validated in a separate cohort recruited from 2 institutions. Of the 124 patients in the derivation cohort, 27% had CAD, including 15% with severe CAD. The independent predictors of severe CAD included diabetes (odds ratio 5.1, p = 0.005), electrocardiographic Q waves or left bundle branch block (odds ratio 3.8, p = 0.02), and ≥2 nondiabetes risk factors: age (men ≥55 or women ≥65 years), dyslipidemia, hypertension, and tobacco use (odds ratio 4.8, p = 0.02). A prediction rule of having ≥1 independent predictor identified 97% of the patients with CAD and 100% of the patients with severe CAD. In the prospective validation cohort of 143 patients, the prediction rule had 98% sensitivity and 18% specificity for CAD but 100% sensitivity for severe CAD. In conclusion, a simple clinical prediction rule can accurately identify patients with CAD and eliminate the need for angiography in a substantial proportion of patients with systolic HF, with potentially significant cost savings and risk avoidance., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Aim of the Study: Currently, few studies have been conducted to assess the outcome patterns of medicolegal cases involving patients with cardiovascular disease. Thus, the literature was reviewed for patterns of liability and medical outcomes in patients involved in aortic stenosis (AS) litigation., Methods: Legal case opinions were obtained from LexisNexis Academic; case characteristics, litigation outcomes, and medical outcomes were identified., Results: Of the 133 cases reviewed, 27% were disability claims, 23% workers' compensation cases, 14% medical malpractice cases, and 9% military service connection cases. Of the 133 cases, only 47% were judged in the patients' favor. The patients' mean age was 48.8 years, and 77% were male. The most common etiology of AS was calcific (38%), followed by rheumatic (31%), bicuspid/congenital (27%), and subaortic (4%). The most common presentation was precordial pain (38%), shortness of breath (35%), syncope/dizziness (18%), fatigue (11%) and death (9%). Aortic valve replacement (AVR) was the most common form of treatment (67%); disability was the most common medical outcome (42%)., Conclusion: AS in litigation follows the standard pattern of AS disease. Only a minority of AS litigation cases are due to medical malpractice, while the majority of AS litigation cases are due to those seeking workers' or disability compensation. Cardiologists treating patients with AS should be cognizant of these litigation patterns and proactively document medical findings, since resulting court decisions profoundly affect the patients' financial means and quality of life.

Research on stereotype threat has demonstrated that when targets are forced to contend with the threat of being negatively stereotyped, their academic performance suffers (C. M. Steele & J. Aronson, 1995). The present research explored how the targets of negative stereotypes determine when they must contend with this threat. Across 5 experiments, the authors manipulated both the possibility and probability that Black and female students would be stereotyped as unintelligent prior to taking an analytical test. Collectively, these experiments showed that these students contended with stereotype threat only when they perceived that it was both possible and probable that they would be negatively stereotyped. The authors discuss the implications of these findings on the experience of being the target of negative stereotypes and on the academic achievement of Blacks and women.

We report a rare case of hepatosplenic abscesses caused by Verticillium spp. in a 40-year-old female leukemic patient. Identification of the microorganism was based on amplification of the D1-D2 region of the large-subunit RNA gene from DNA extracted from paraffin sections of liver tissue, followed by sequencing of the amplified polymerase chain reaction product.

Purpose: The molecular mechanism involved in the hypertrophy of the orbital fat in patients with Graves' ophthalmopathy or thyroid eye disease (TED) remains unclear. Comparison of genome-wide expression profiles may help in the search for the gene sets involved in TED., Methods: Twenty-five orbital adipose tissue specimens were obtained, from which the RNA was isolated. Four of the tissue specimens (from four individuals, two with TED and two control subjects) were subjected to cDNA microarray analysis. The data were analyzed by the gene set enrichment analysis (GSEA) to survey the biological pathways involved in the pathogenesis of TED. Messenger RNA levels of some top-ranked genes in GSEA-selected pathways are validated by quantitative PCR (QPCR)., Results: The expression of specific gene sets related to lytic vacuoles, lysosomes, and vacuoles were different between the specimens obtained from patients with TED and control subjects (P < 0.001). These three gene sets overlapped. For QPCR, four top-ranked genes were selected from these overlapping gene sets and another one that related to visual failure, using 21 independent samples of patients with TED (n = 15) and control subjects (n = 6). The results showed that ceroid-lipofuscinosis, neuronal 2, late infantile (CLN2; P = 0.044) and ceroid-lipofuscinosis, neuronal 3, juvenile (CLN3, which related to visual failure; P = 0.012) were significantly downregulated in the orbital fat of patients with TED. The expression of the beta subunit of hexosaminidase A (HEXB) was reduced as well, but the change did not reach statistical significance (P = 0.058)., Conclusions: Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED.

Tissue remodeling associated with thyroid-associated ophthalmopathy (TAO) involves the complex interplay between resident cells (endothelium, vascular smooth muscle, extraocular muscle, and fibroblasts) and those recruited to the orbit, including members of the "professional" immune system. Inflammation early in the disease can later culminate in fibrosis and diminished extraocular muscle motility. TAO remains a poorly understood process, in large part because access to tissues early in the disease is limited and because no robust and complete animal models of Graves' disease have yet been devised. Remaining uncertainty as to the identity of a pathogenic autoantigen(s) that underlies lymphocyte trafficking to the orbit complicates matters. These limitations in our understanding of extrathyroidal Graves' disease have resulted in poorly served patients with severe TAO. Therapies have targeted symptoms rather than the underlying disease processes. Our laboratory group has focused over the last several years on defining the peculiarities of the human orbital fibroblasts as a strategy for shedding more light on the pathologies occurring in TAO. We have reasoned that unique properties of these cells might ultimately prove the basis for why the manifestations of Graves' disease occur in an anatomically selective manner. In this brief review we attempt to survey our findings. We believe that they might provide a "roadmap" for further discovery into the pathogenesis of TAO. Clearly, more questions remain than those thus far answered.

Background and Purpose: Acinetobacter baumannii is an important nosocomial pathogen. Bacteremia caused by multidrug-resistant A. baumannii (MDRAB) leads to higher mortality and medical cost compared with non-MDRAB bacteremia. We aimed to identify risk factors of multidrug resistance in A. baumannii bacteremia., Methods: A matched case-control study was conducted to compare the differences in risk factors of patients with MDRAB and non-MDRAB bacteremia., Results: Sixty three patients with MDRAB bacteremia and 63 matched patients with non-MDRAB bacteremia were identified from hospital and laboratory records of the period 1996 to 2002. Multivariate logistic regression analysis identified four independent risk factors associated with multidrug resistance in A. baumannii bacteremic patients: previous colonization with A. baumannii (odds ratio [OR], 7.99; 95% confidence interval [CI], 2.1-30.6; p=0.002), antecedent antimicrobial therapy (OR, 6.10; 95% CI, 1.2-29.9; p=0.026) the number of recently prescribed antibiotics (OR 1.35; 95% CI, 1.0-1.8; p=0.026), and recent invasive procedures (OR, 4.17; 95% CI, 1.6-11.1; p=0.004)., Conclusions: Overall, patients with MDRAB bacteremia had earlier A. baumannii colonization, greater previous exposure to antimicrobial agents and recent invasive procedures. The results of this study demonstrate a rationale for the development of effective interventions to minimize the impact of MDRAB.

Adult tilapia were exposed to 0 (control) and 4.45 microM Cd for 0 h, 5 h, 5 days, and 15 days, and the physiological responses of fish were described. The physiological responses were first expressed in gill tissue, in which mucus cells secretion increased, Cd accumulated, cortisol secretion was significantly higher, but serum ACH(50) activity (alternative complement hemolytic assay) was significantly lower than in controlled fish. After 5 days of Cd exposure, the ACH(50) activity showed a greater decrease, but lysozyme and cortisol contents showed significant increases over the control. Cd levels significantly increased in intestines, liver, and kidneys, and a significant induction of metallothionein (MT) protein in hepatic tissue was noted. Finally, the Cd accumulation rate still showed significant increases in these organs. However, the MT content was similar at 5 days and at 15 days after Cd exposure, and the cortisol contents had recovered to the pre-exposure level. In addition, Cd accumulation in muscle was higher after Cd exposure than in controls (t-test, p<0.05). Our results demonstrate (1) that tilapia readily regulate their physiological parameters in order to acclimate to a sublethal Cd environment; (2) these changes of physiological parameters may be related with a succession of cortisol levels following Cd exposure; (3) increasing rate of hepatic MT contents and Cd accumulation rate didn't appear identical after 5-15 days of Cd exposure. This was confirmed that hepatic MT was not a good indicator for Cd levels in tilapia.

The objectives of this study were to try to determine the reasons of the external Ca(2+) and Na(+) enhancement of Cd(2+) and Cu(2+) resistance in fish. Tilapia larvae at 3 days posthatch were exposed to (A) 0 (control), 40 microg/L Cd(2+), 40 microg/L Cd(2+) + 2 mM Ca(2+) (Cd/hyper-Ca), and 2 mM Ca(2+) or (B) 0 (control), 75 microg/L Cu(2+), 75 microg/L Cu(2+) + 0.52 mM Na(+) (Cu/hyper-Na), and 0.52 mM Na(+). After 48 hours, results indicated that (1) Cd/hyper-Ca and Cu/hyper-Na treatments showed decreased growth inhibition induced by the metals; (2) metal accumulation in Cd/hyper-Ca-treated larvae was lower compared with those exposed only to Cd; and (3) metallothionein (MT) expression was significantly higher in Cu/hyper-Na-treated larvae than in the group treated with Cu only. Taking all of this into account, either supplementary Ca(2+) or Na(+) in ambient water may help fish to maintain Ca(2+) or Na(+) homeostasis, which could decrease metal accumulation and its detrimental effects. Consequently, the fish increase MT expression and retard the growth inhibition caused by metals.

Background: Numerous studies have suggested that high-frequency oscillatory ventilation (HFOV) used as rescue therapy may improve oxygenation in acute respiratory distress syndrome (ARDS) patients. The purpose of this study is to analyze the efficacy and safety of HFOV in surgical patients with ARDS., Methods: A total of 16 surgical ARDS patients with severe oxygenation failure received HFOV, despite aggressive conventional mechanical ventilatory support. Mean airway pressure was initially set 3 to 5 cm H2O higher than that for conventional ventilation and was subsequently adjusted to maintain oxygen saturation > or = 90% and FiO2 < or =0.6. Oxygenation, ventilation, and hemodynamic parameters were measured during conventional ventilation before initiating HFOV and during HFOV support for a total of 40 hours. Other outcome measures included duration of HFOV, successful weaning rate, cause of failure, complications, survival rate, and cause of death., Results: There was a considerable increase in Pao2/FiO2 ratio after 30 minutes, and this increase was maintained after 12 hours of HFOV throughout the study. There was a significant decrease in oxygenation index after 24 hours of HFOV support. There was no significant change in blood pressure associated with initiation and administration of HFOV. The successful weaning rate from HFOV to conventional ventilation was 75%. The intensive care unit survival rate was 43.8% and hospital survival rate was 37.5%., Conclusion: High-frequency oscillatory ventilation was effective and safe in correcting oxygenation failure associated with ARDS in surgical patients. Future research is warranted to identify the suitable patients, timing, and optimal strategy for applying HFOV.

Background/purpose: Postoperative diplopia remains a significant complication of orbital decompression in dysthyroid orbitopathy. This study evaluated the results of orbital decompression treatment using a transforniceal approach to sculpt the lateral orbital deep bone area., Methods: The two areas of bone in the deep lateral orbit (the basin of the inferior orbital fissure and the sphenoid door jamb) were exposed using a transforniceal swinging eyelid approach. An electric drill was used to sculpt these deep bone areas of the lateral orbit, and approximately 1 mL intraconal fat was removed simultaneously. Between October 1999 and March 2003, transforniceal lateral deep bone decompression was performed in 35 consecutive patients (62 orbits) with disfiguring dysthyroid orbitopathy. Data on proptosis reduction effect, new-onset diplopia and other complications of lateral wall decompression were analyzed., Results: The average preoperative Hertel value was 21.2 +/- 1.3 mm (range, 18-23 mm) and decreased to 17.4 +/- 1.2 mm (range, 15-19.5 mm) postoperatively. The mean decrease in proptosis 3 months postoperatively was 3.8 +/- 0.91 mm (range, 1.5-4.6 mm). New-onset downgaze diplopia occurred in two (5.7%) of the 35 patients. Persistent trigeminal paresthesia was noted in one patient (2.8%). No cerebrospinal fluid leak, globe injury or vision deterioration was noted during 9.5 +/- 1.7 months of follow-up. The cosmetic appearance was improved in all patients after surgery., Conclusion: Transforniceal lateral deep bone decompression produces less new-onset, persistent diplopia than traditional inferomedial wall decompression, and provides good cosmesis by using a hidden small incisional wound. This approach appears to be a safe and effective procedure for patients with disfiguring exophthalmos, especially for Asian patients without crease fold.

Context: Upper lid retraction is a common sign in Graves' ophthalmopathy (GO). Whether Müller's muscle is involved in upper lid retraction has not been fully elucidated., Objective: The objective of the study was to understand the molecular pathology of Müller's muscle in GO., Design/setting/participants: A method for measurement of histological changes was developed and used to correlate severity and expression of cell-specific genes in GO., Main Outcome Measures: Histological changes, clinical severity of upper lid retraction, and mRNA expression in Müller's muscle in GO were measured., Results: The degree of fibrosis correlates with severity of upper lid retraction. Macrophage infiltration was increased in fibrotic areas, consistent with higher levels of macrophage-colony stimulating factor mRNA. Levels of peroxisome proliferator-activated receptor-gamma mRNA were up-regulated and correlated with fat infiltration. Decreased muscle mass correlated with lower myocardin mRNA expression. The expression of c-kit levels was decreased in diseased muscles, consistent with diminished mast cell numbers., Conclusion: The pathological changes of Müller's muscle correlate with clinical severity of upper lid retraction in GO. Patterns of gene expression appear to correlate with the histopathological changes in this disease process.

Purpose: To determine whether complete detachment of the fascia of the capsulopalpebral head during large inferior rectus recession can help to prevent induced lower lid retraction in Graves ophthalmopathy., Design: Retrospective consecutive case series., Methods: Data from patients (39 eyes) with Graves ophthalmopathy undergoing inferior rectus recession were collected retrospectively. Inferior rectus recession was performed by limbus-based incision with adjustable suture. Simultaneous detachment of the fascia of the capsulopalpebral head was achieved by sharp dissection and severing of the fascia. Inferior rectus recession with simultaneous detachment of the fascia of the capsulopalpebral head was performed in 27 eyes and without detachment in 12 eyes. Margin reflex distance (MRD2) was documented preoperatively and 3 months postoperatively., Results: Of the 39 eyes included in this study, four eyes with preexisting lower lid retraction in the detachment group improved after surgery. Eighteen eyes in the detachment group exhibited the same MRD2 values, and only five eyes showed increased MRD2 values. In contrast, all but one of the 12 eyes in the nondetachment group showed increased MRD2 values. The average change in the MRD2 value 3 months after surgery was 0.04+/-0.59 mm in the detachment group and 1.58+/-0.73 mm in the nondetachment group. There was a statistically significant difference between the two groups (P<.01)., Conclusions: Simultaneous detachment of the fascia of the capsulopalpebral head during inferior rectus recession can minimize the possibility of lower lid retraction.

Dying microbes and necrotic cells release highly viscous DNA that induces inflammation and septic shock, and apoptotic cells display DNA, a potential autoantigen, on their surfaces. However, innate immune proteins that mediate the clearance of free DNA and surface DNA-containing cells are not clearly established. Pulmonary surfactant proteins (SP-) A and D are innate immune pattern recognition collectins that contain fibrillar collagen-like regions and globular carbohydrate recognition domains (CRDs). We have recently shown that collectins SP-A, SP-D, and mannose binding lectin recognize DNA and RNA via their collagen-like regions and CRDs. Here we show that SP-D enhances the uptake of Cy3-labeled fragments of DNA and DNA-coated beads by U937 human monocytic cells, in vitro. Analysis of DNA uptake by freshly isolated mouse alveolar macrophages shows that SP-D, but not SP-A, deficiency results in reduced clearance of DNA, ex vivo. Analysis of bronchoalveolar lavage fluid shows that SP-D- but not SP-A-deficient mice are defective in clearing free DNA from the lung. Additionally, both SP-A- and SP-D-deficient mice accumulate anti-DNA Abs in sera in an age-dependent manner. Thus, we conclude that collectins such as SP-A and SP-D reduce the generation of anti-DNA autoantibody, which may be explained in part by the defective clearance of DNA from the lungs in the absence of these proteins. Our findings establish two new roles for these innate immune proteins and that SP-D enhances efficient pinocytosis and phagocytosis of DNA by macrophages and minimizes anti-DNA Ab generation.

Purpose: To study a new surgical option of primary placement of a hydroxyapatite-coated sleeve into the Bioceramic implant during enucleation or evisceration., Design: Retrospective, observational case series., Methods: A standard enucleation or evisceration was performed, followed by the preplacement of a hydroxyapatite-coated sleeve into the Bioceramic implant. Care must be taken to ensure the sleeve has been positioned centrally when the implant is put inside the orbital socket. Complications such as sleeve exposure, Bioceramic implant exposure, and infection were closely observed., Results: Twenty-seven patients were treated in above fashion with five enucleation and 22 evisceration procedures. Five of the sleeves have exposed spontaneously during 1 to 4 months after original surgery. They had no further complication, except for one sleeve around which there were visible Bioceramic spicules attributable to long-term corticosteroid usage. The remaining 22 sleeves that did not spontaneously expose pursued secondary exposure of the sleeve and peg insertion by the conjunctival cutdown procedure 3 months postoperatively. One sleeve was medially positioned far away from the implant center. Re-insertion of new sleeve and peg was scheduled 2 weeks later. One additional sleeve was obliquely positioned after conjunctival cutdown procedure. Fortunately, all 27 patients were successfully fitted with a peg-coupled prosthesis with good motility., Conclusions: Primary placement of a hydroxyapatite-coated sleeve into the Bioceramic implants has several advantages, including high patient acceptance, technical simplicity, and an office-based conjunctival cutdown pegging procedure. By avoiding the expense of postoperative imaging studies and additional prosthetic modification, a more rapid and efficient rehabilitation is possible.

Collectins are a family of innate immune proteins that contain fibrillar collagen-like regions and globular carbohydrate recognition domains (CRDs). The CRDs of these proteins recognize various microbial surface-specific carbohydrate patterns, particularly hexoses. We hypothesized that collectins, such as pulmonary surfactant proteins (SPs) SP-A and SP-D and serum protein mannose-binding lectin, could recognize nucleic acids, pentose-based anionic phosphate polymers. Here we show that collectins bind DNA from a variety of origins, including bacteria, mice, and synthetic oligonucleotides. Pentoses, such as arabinose, ribose, and deoxyribose, inhibit the interaction between SP-D and mannan, one of the well-studied hexose ligands for SP-D, and biologically relevant d-forms of the pentoses are better competitors than the l-forms. In addition, DNA and RNA polymer-related compounds, such as nucleotide diphosphates and triphosphates, also inhibit the carbohydrate binding ability of SP-D, or approximately 60 kDa trimeric recombinant fragments of SP-D that are composed of the alpha-helical coiled-coil neck region and three CRDs (SP-D(n/CRD)) or SP-D(n/CRD) with eight GXY repeats (SPD(GXY)(8)(n/CRD)). Direct binding and competition studies suggest that collectins bind nucleic acid via their CRDs as well as by their collagen-like regions, and that SP-D binds DNA more effectively than do SP-A and mannose-binding lectin at physiological salt conditions. Furthermore, the SP-D(GXY)(8)(n/CRD) fragments co-localize with DNA, and the protein competes the interaction between propidium iodide, a DNA-binding dye, and apoptotic cells. In conclusion, we show that collectins are a new class of proteins that bind free DNA and the DNA present on apoptotic cells by both their globular CRDs and collagen-like regions. Collectins may therefore play an important role in decreasing the inflammation caused by DNA in lungs and other tissues.

Purpose: To evaluate the safety and efficacy of injections with botulinum toxin type A (BTTA,Botox), given transcutaneously, in the treatment of upper lid retraction associated with thyroid eye disease (TED)., Methods: A total of 15 patients (21 eyes) with a stable (TED) condition, and a euthyroid state, were enrolled into the study. There were 12 females and three males from ages 23 to 52 years. A single injection, at the centrally superior tarsal border transcutaneously, aiming at the levator aponeurosis and Müller muscle, was administered into each eyelid with 5-6 U of Botox. All patients were followed regularly for 4-6 months. Any complications, such as ptosis, diplopia, pain,or lid ecchymosis were recorded., Results: All patients, except one, experienced much reduction of palpebral fissure. The mean difference of MRD1 between pre- and postinjections of Botox at the first week was -3.1 mm, and the effect remained, at least, for 2 months. There were temporary complications of ptosis in three patients and vertical diplopia in two patients, lasting 3-4 weeks., Conclusions: A single transcutaneous injection with Botox for the treatment of thyroid lid retraction is safe and effective. Some minor complications may occur, such as ptosis and diplopia; however, it may offer an alternative and temporary method for patients with dysthyroid lid retraction, who are waiting for a staged operation of either an orbital decompression or a strabismus surgery or both.

Background: In patients with acute respiratory distress syndrome, whether inverse ratio ventilation differs from high positive end-expiratory pressure (PEEP) for gas exchange under a similar mean airway pressure has not been adequately examined. The authors used arterial oxygenation, gastric intramucosal partial pressure of carbon dioxide (PiCO(2)), and pH (pHi) to assess whether pressure-controlled inverse ratio ventilation (PC-IRV) offers more benefits than pressure-controlled ventilation (PCV) with PEEP., Methods: Seventeen acute respiratory distress syndrome patients were enrolled and underwent mechanical ventilation with a PCV inspiratory-to-expiratory ratio of 1:2, followed by PC-IRV 1:1 initially. Then, they were randomly assigned to receive PC-IRV 2:1, then 4:1 or 4:1, and then 2:1, alternately. The baseline setting of PCV 1:2 was repeated between the settings of PC-IRV 2:1 and 4:1. Mean airway pressure and tidal volume were kept constant by adjusting the levels of peak inspiratory pressure and applied PEEP. In each ventilatory mode, hemodynamics, pulmonary mechanics, arterial and mixed venous blood gas analysis, PiCO(2), and pHi were measured after a 1-h period of stabilization., Results: With a constant mean airway pressure, PC-IRV 2:1 and 4:1 decreased arterial and mixed venous oxygenation as compared with baseline PCV 1:2. Neither the global oxygenation indices with oxygen delivery and uptake nor PiCO(2) and pHi were improved by PC-IRV. During PC-IRV, applied PEEP was lower, and auto-PEEP was higher., Conclusion: When substituting inverse ratio ventilation for applied PEEP to keep mean airway pressure constant, PC-IRV does not contribute more to better gas exchange and gastric intramucosal PiCO(2) and pHi than does PCV 1:2 for acute respiratory distress syndrome patients, regardless of the inspiratory-to-expiratory ratios.

In a systematic effort to develop a microbicide contraceptive capable of preventing transmission of human immunodeficiency virus (HIV), as well as providing fertility control, we have previously identified novel phenyl phosphate derivatives of zidovudine (ZDV) with 5-halo 6-alkoxy substitutions in the thymine ring and halo substitution in the phenyl moiety respectively. Here, we describe the synthesis, characterization, and successful preclinical formulation of our lead compound, 5-bromo-6-methoxy-3'-azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate (WHI-07), which exhibits potent anti-HIV and sperm immobilizing activities. The anti-HIV activity of WHI-07 was tested by measuring viral p24 antigen production and reverse transcriptase activity as markers of viral replication in HIV-1 infected human peripheral blood mononuclear cells (PBMC). WHI-07 inhibited replication of HIV in a concentration-dependent fashion with nanomolar IC50 values. The effects of WHI-07 on human sperm motion kinematics were analysed by computer-assisted sperm analysis (CASA), and its effects on sperm membrane integrity were examined by confocal laser scanning microscopy (CLSM), and high-resolution low-voltage scanning electron microscopy (HR-LVSEM). WHI-07 caused cessation of sperm motility in a concentration- and time-dependent fashion. The in-vitro cytotoxicities of WHI-07 and nonoxynol-9 (N-9) were compared using normal human ectocervical and endocervical epithelial cells by the MTT cell viability assay. Unlike N-9, WHI-07 had no effect upon sperm plasma and acrosomal membrane integrity. N-9 was cytotoxic to normal human ectocervical and endocervical cells at spermicidal doses, whereas WHI-07 was selectively spermicidal. The in-vivo vaginal absorption and vaginal toxicity of 2% gel-microemulsion of WHI-07 was studied in the rabbit model. The sperm immobilizing activity of WHI-07 was 18-fold more potent than that of N-9. Over a 10 day period, there was no irritation or local toxicity to the vaginal epithelia or systemic absorption of WHI-07. Therefore, as a potent anti-HIV agent with spermicidal activity, and lack of mucosal toxicity, WHI-07 may have the clinical potential to become the active ingredient of a vaginal contraceptive for women who are at high risk for acquiring HIV by heterosexual vaginal transmission.

The potency and selectivity index of the AZT-phenyl phosphate derivatives in thymidine kinase (TK)-deficient T cells were substantially enhanced by introducing a single para-bromo substitutent in the phenyl moiety. AZT-5'-(p-bromophenyl methoxyalaninyl phosphate) was 43-fold more potent than AZT-5'-(phenyl methoxyalaninyl phosphate) and was fivefold more potent than AZT in inhibiting human immunodeficiency virus (HIV) replication in TK-deficient CEM cells.

We synthesized a novel compound, 5-bromo-6-methoxy-5,6-dihydro-AZT-5'- (p-bromophenyl methoxyalaninyl phosphate), which had an EC50 value of 5 microM in sperm motility assays. This is > 1 log10 better than that of the detergent spermicide nonoxynol-9 (EC50 81 microM). The compound also displayed a potent anti-human immunodeficiency virus (HIV) activity with an IC50 value of 0.005 microM in HIV replication assays, which was virtually identical to that of AZT (IC50 0.006 microM) and > 2 log10 more potent than that of nonoxynol-9 (IC50 2.2 microM). The promising results reported herein recommend the further development of the dual function 5-halo-6-alkoxyl-5,6-dihydro-AZT derivatives as a new class of vaginal contraceptives capable of preventing the sexual transmission of HIV while providing fertility control for women who are at high risk of acquiring HIV by heterosexual transmission. These dual function 5-halo-6-alkoxyl-5,6-dihydro-AZT derivatives may also have utility in curbing domestic and wildlife animal retroviral transmissions.

Detergent-based vaginal microbicides, in addition to their high contraceptive failure rates, cause mucosal erosion and local inflammation that might increase the risk of heterosexual human immunodeficiency virus (HIV) transmission. In a systematic effort to identify a microbicide contraceptive potentially capable of preventing the sexual transmission of HIV as well as providing fertility control, a series of novel aryl phosphate derivatives of 5-bromo-6-methoxy-3'-azido-3'-deoxythymidine (AZT; zidovudine) were synthesized and examined for dual anti-HIV and sperm-immobilizing activity (SIA). Whereas AZT displayed potent anti-HIV activity (IC50 = 0.006 microM) but lacked SIA (EC50 > 300 microM), two 5-bromo-6-methoxy-aryl phosphate derivatives of AZT, compounds WHI-05 and WHI-07, exhibited potent anti-HIV activity as well as SIA. The IC50 (HIV) and EC50 (SIA) values for WHI-07 were 439-fold and 13.5-fold lower, respectively, than those for the detergent-based virucidal spermicide, nonoxynol-9 (N-9). Sperm motion kinematics using computer-assisted sperm motion analysis combined with confocal laser scanning microscopy, high-resolution low-voltage scanning, and transmission electron microscopy demonstrated that both WHI-05 and WHI-07 cause a complete and irreversible loss of sperm motility in a concentration- and time-dependent fashion without concomitantly affecting the sperm acrosomal membrane integrity. In experiments designed to assess the fertilizing capacity of treated sperm, preincubation of sperm with either compound resulted in a concentration-dependent loss of the ability to adhere to and penetrate zona-free hamster eggs as well as inhibition of binding to human zona. WHI-07 applied intravaginally prior to artificial insemination of epididymal sperm drastically reduced fertility in hormonally primed CD-1 mice. Unlike the intravaginal application of N-9, repetitive intravaginal application of WHI-07 did not damage the vaginal epithelium or cause local inflammation. Structure-function relationship analyses showed that the addition of bromo-methoxy functional groups to AZT was essential for, and the aryl phosphate derivatization contributory to, the SIA of both compounds. Compounds WHI-05 and WHI-07 may be useful as dual-function vaginal contraceptives for women who are at high risk for acquiring HIV/acquired immunodeficiency virus syndrome by heterosexual vaginal transmission.

The diffusion-dependent kinetic properties of the yeast glyoxalase I reaction have been measured by means of viscosometric methods. For the glyoxalase-I-catalyzed isomerization of glutathione (GSH)-methylglyoxal thiohemiacetal to S-D-lactoylglutathione, the k(cat)/Km (3.5 x 10(6) M(-1) s(-1), pH 7, 25 degrees C) undergoes a progressive decrease in magnitude with increasing solution viscosity, using sucrose as a viscogenic agent. The viscosity effect is unlikely to be due to a sucrose-induced change in the intrinsic kinetic properties of the enzyme, as the magnitude of k(cat)/Km for the slow substrate GSH-t-butylglyoxal thiohemiacetal (3.5 x 10(3) M(-1) s(-1), pH 7, 25 degrees C) is independent of solution viscosity. Quantitative treatment of the data by means of the Stokes-Einstein diffusion law suggests that catalysis will be about 50% diffusion limited under conditions where [substrate] << Km; the encounter complex between enzyme and substrate partitions nearly equally between product formation and dissociation to form free enzyme and substrate. In a related study, the steady-state concentrations of glyoxalase-pathway intermediates in glycolyzing human erythrocytes are estimated to be in the nanomolar concentration range, on the basis of published values for the activities of glyoxalase I and glyoxalase II in lysed erythrocytes and the steady-state rate of formation of D-lactate in intact erythrocytes. This is consistent with a model of the glyoxalase pathway in which the enzyme-catalyzed steps are significantly diffusion limited under physiological conditions.

We used a precision two-circle goniometer mounted to the stage of a compound microscope to determine the optical alignment and to measure the entrance aperture diameter of individual cuticular cones in the dioptric array of the lateral eye of juvenile horseshoe crabs in order to learn about the development of the visual field. Our results show that the extent of the visual field of juvenile horseshoe crabs with prosomal lengths about 20% of adult size (14-21 mm) is about 70% that of the visual field of adult horseshoe crabs (prosomal lengths: 100+ mm). The visual field of such juvenile animals covers between 77 and 85 deg vertically and 140 and 145 deg horizontally. Assuming that the dioptric array is uniform and square packed, the average interommatidial angle of the juvenile animals is between 5.6 and 6.0 deg as compared to 4.6 deg for an adult animal. The diameter of the entrance aperture of individual cuticular cones increases markedly with increasing animal size. In addition, we noted a statistically significant trend for entrance aperture diameters to increase from anterior to posterior within the eye for animals of all sizes. There may be a slight trend for entrance aperture diameters to increase from dorsal to ventral within the eye. Our results indicate that the extent of the visual field and the resolution of the lateral eye approach adult values in advance of animals' reaching sexual maturity.

The dimeric formaldehyde dehydrogenase from bovine liver has been resolved into three nearly homogeneous enzyme forms by the successive use of ion-exchange, affinity, and ampholine (chromatofocusing) chromatography. The different enzyme species were isolated in the approximate proportions 3:2:1, having pI values of 6.5, 6.2, and 6.0, respectively. The subunit molecular weights of the three forms are all similar (Mr congruent to 41,000), on the basis of sodium dodecyl sulfategel electrophoresis. The enzyme species appear to arise from covalent differences unrelated either to partial proteolysis during isolation or to differential sialization of homodimeric protein. Human liver contains a single major form and two minor forms of formaldehyde dehydrogenase having pI values very similar to those found for the bovine liver enzyme. The macroscopic kinetic constants (V, V/K) for the three forms of the dehydrogenase from bovine liver are all similar in magnitude, using NADH and S-hydroxymethylglutathione as substrates. The isotope-sensitive hydride transfer step is not significantly rate-limiting during catalysis by any of the forms, as evidenced by the near-unity primary deuterium isotope effects on both V and V/KS (for S-hydroxymethylglutathione); catalysis may be limited by the rate of dissociation of at least one (and possibly both) of the product molecules. In support of rate-limiting dissociation of NAD+ in the normal reaction, V increases by approximately 22-fold and isotope effects of approximately 1.4 are observed on both V and V/KS, using the coenzyme analog 3-acetylpyridine adenine dinucleotide. Product dissociation from the active site appears to be accelerated by the presence of dilute denaturing agents, perhaps indicative of a rate-limiting conformational transition associated with product release.

We have synthesized the (19R)- and (19S)-isomers (2 and 3 respectively) of 10 beta-oxiranylestr-4-ene-3,17-dione. The configurations and conformations of these compounds were established by X-ray crystallographic analysis. Each of these compounds is a powerful competitive inhibitor of human placental microsomal aromatase, and stereoselectivity of inhibition was observed (Ki values for 2 and 3 were 7 and 75 nanomolar, respectively). Spectroscopic studies with purified aromatase indicate that the inhibition process involves reversible binding of oxirane oxygen to the heme iron of the enzyme. The (19R)- and (19S)-10 beta-thiiranes (6 and 7) corresponding to 2 and 3 have been synthesized from the oxiranes by a stereospecific process. The thiiranes are very effective competitive inhibitors of placental aromatase, and show even greater stereoselectivity in binding than the oxiranes (Ki values for 6 and 7 were 1 and 75 nanomolar, respectively). Spectroscopic studies with purified aromatase indicate that the inhibition process involves reversible binding of thiirane sulfur to heme iron.