Safety and feasibility comparison between three different CT-guided localization techniques under systemic approach algorithm.

INTRODUCTION: In the era of lung cancer screening, more and more sub-centimeter indeterminate lung lesions are being identified. It is difficult to approach these lesions and obtain tissue to confirm diagnosis. CT-guided navigation followed by surgical resection is the best way to overcome this difficulty. The aim of this study is to compare the safety and feasibility of wire and dye-tattoo CT-guided localization techniques. MATERIALS AND METHODS: From September 2019 to August 2021, 418 patients who presented with single lung lesion and received single CT-guided localization were included in this study. Procedure details, navigation results, and related complications were compared. RESULTS: For patients who received wire localization, majority (98.3 %) had perihilar lesions. In addition, 68 (57.1 %) patients received tangential approach because of lesions were blocked by bony or vital structure, abutting major fissure, or previous approach failure. The characteristics of lesion location was quite different than dye-tattooing technique (p = 0.033). As regards persistence of the target lesion localization, the interval between localization and surgery using ICG tattooing was 829.0 ± 552.9 min; much longer than the other two navigation techniques (p < 0.0001). As regards safety, patients who received wire localization had a higher rate of pneumothorax (p = 0.042) and pulmonary hemorrhage (p < 0.001) than the dye-tattooing techniques. DISCUSSION: CT-guided navigation techniques are safe and feasible. Wire localization is suitable for centrally located lesions but the wire needs to be fixed properly and symptomatic pneumothorax monitored for. Dye-tattooing is more suitable for peripheral lesions, while ICG localization persists longer than other techniques.

Effects of different dual task training on dual task walking and responding brain activation in older adults with mild cognitive impairment.

The concurrent additional tasking impacts the walking performance, and such impact is even greater in individuals with mild cognitive impairment (MCI) than in healthy elders. However, effective training program to improve dual task walking ability for the people with MCI is not immediately provided. Therefore, this study aimed to determine the effects of cognitive and motor dual task walking training on dual task walking performance and the responding brain changes in older people with MCI. Thirty older adults with MCI were randomly allocated to receive 24 sessions of 45-min cognitive dual task training (CDTT, n = 9), motor dual task training (MDTT, n = 11), or conventional physical therapy (CPT, n = 10). Gait performance and brain activation during single and dual task walking, and cognitive function assessed by trail-making test (TMT-A, B) and digit span test were measured at pre-, post-test, and 1-month follow-up. Both CDTT and MDTT improved dual task walking with responding activation changes in specific brain areas. The improvements in motor dual task walking performance after both dual task trainings were significantly better than after CPT in the older adults with MCI. Both cognitive and motor dual task training were feasible and beneficial to improve dual task walking ability in older adults with MCI.Trial Registration: The trial was registered to Thai Clinical Trial Registry and the registration number is TCTR20180510002 (first registration date: 10/05/2018).

Predictors of Invasive Adenocarcinomas among Pure Ground-Glass Nodules Less Than 2 cm in Diameter.

Benign lesions, atypical adenomatous hyperplasia (AAH), and malignancies such as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA) may feature a pure ground-glass nodule (pGGN) on a thin-slide computed tomography (CT) image. According to the World Health Organization (WHO) classification for lung cancer, the prognosis of patients with IA is worse than those with AIS and MIA. It is relatively risky to perform a core needle biopsy of a pGGN less than 2 cm to obtain a reliable pathological diagnosis. The early and adequate management of patients with IA may provide a favorable prognosis. This study aimed to disclose suggestive signs of CT to accurately predict IA among the pGGNs. A total of 181 pGGNs of less than 2 cm, in 171 patients who had preoperative CT-guided localization for surgical excision of a lung nodule between December 2013 and August 2019, were enrolled. All had CT images of 0.625 mm slice thickness during CT-guided intervention to confirm that the nodules were purely ground glass. The clinical data, CT images, and pathological reports of those 171 patients were reviewed. The CT findings of pGGNs including the location, the maximal diameter in the long axis (size-L), the maximal short axis diameter perpendicular to the size-L (size-S), and the mean value of long and short axis diameters (size-M), internal content, shape, interface, margin, lobulation, spiculation, air cavity, vessel relationship, and pleural retraction were recorded and analyzed. The final pathological diagnoses of the 181 pGGNs comprised 29 benign nodules, 14 AAHs, 25 AISs, 55 MIAs, and 58 IAs. Statistical analysis showed that there were significant differences among the aforementioned five groups with respect to size-L, size-S, and size-M (p = 0.029, 0.043, 0.025, respectively). In the univariate analysis, there were significant differences between the invasive adenocarcinomas and the non-invasive adenocarcinomas with respect to the size-L, size-S, size-M, lobulation, and air cavity (p = 0.009, 0.016, 0.008, 0.031, 0.004, respectively) between the invasive adenocarcinomas and the non-invasive adenocarcinomas. The receiver operating characteristic (ROC) curve of size for discriminating invasive adenocarcinoma also revealed similar area under curve (AUC) values among size-L (0.620), size-S (0.614), and size-M (0.623). The cut-off value of 7 mm in size-M had a sensitivity of 50.0% and a specificity of 76.4% for detecting IAs. In the multivariate analysis, the presence of air cavity was a significant predictor of IA (p = 0.042). In conclusion, the possibility of IA is higher in a pGGN when it is associated with a larger size, lobulation, and air cavity. The air cavity is the significant predictor of IA.

A Muscle Biosignature Differentiating Between Limb-Girdle Muscular Dystrophy and Idiopathic Inflammatory Myopathy on Magnetic Resonance Imaging.

Background: The overlapping clinical presentations of limb-girdle muscular dystrophy (LGMD) and idiopathic inflammatory myopathy (IIM) make clinical diagnosis challenging. This study provides a comprehensive evaluation of the distributions and characteristics of muscle fat substitution and edema and aims to differentiate those two diseases. Methods: This retrospective study reviewed magnetic resonance imaging (MRI) of seventeen patients with pathologically proved diagnosis, comprising 11 with LGMD and 6 with IIM. The fat-only and water-only images from a Dixon sequence were used to evaluate muscle fat substitution and edema, respectively. The degrees of muscle fat substitution and edema were graded and compared using the appropriate statistical methods. Results: In LGMD, more than 50% of patients had high-grade fat substitution in the majority of muscle groups in the thigh and calf. However, <50% of IIM patients had high-grade fat substitution in all muscle groups. Moreover, LGMD patients had significantly higher grade fat substitution than IIM patients in all large muscle groups (p < 0.05). However, there was no significant difference in edema in the majority of muscle groups, except the adductor magnus (p = 0.012) and soleus (p = 0.009) with higher grade edema in IIM. Additionally, all the adductor magnus muscles in LGMD (100%) showed high-grade fat substitution, but none of them showed high-grade edema. Conclusions: MRI could be a valuable tool to differentiate LGMD from IIM based on the discrepancy in muscle fat substitution, and the adductor magnus muscle could provide a biosignature to categorizing LGMD.

Back massage intervention for improving health and sleep quality among intensive care unit patients.

BACKGROUND: A massage may relax muscles, improve blood circulation and reduce pain and anxiety while also improving sleep quality by increasing comfort. However, there is little research on whether a back massage improves sleep quality in intensive care unit (ICU) patients. AIMS AND OBJECTIVES: This study examined the effects of a back massage on improving vital signs, sleep quality, anxiety and depression among ICU patients. DESIGN: Adopting a quasi-experimental design, convenience sampling was used to recruit ICU patients from a medical centre in Southern Taiwan. The experimental group received back massages for three consecutive days (n = 30), while controls received usual care (n = 30). METHODS: The Verran and Snyder-Halpern Scale and the Hospital Anxiety and Depression Scale were used, and subjective and objective sleep time (wrist actigraphy and sleep duration from nurse observations) was recorded. The effect of the intervention was examined using a generalized estimating equation model with a robust standard error and an exchangeable working correlation matrix adjusting for time. RESULTS: The results show that subjective sleep quality scores in ICU patients were low. Mean observed sleep time (measured by nurses) was 3·9 h, but mean sleep time measured using wrist actigraphy was 5·9 h. Back massages improved breathing in patients, increased sleep quality reflected by both subjective and objective data and were associated with a significant change in anxiety. CONCLUSIONS: These findings suggest that a 10-min back massage can improve sleep quality, sleep duration, breathing and anxiety in ICU patients. RELEVANCE TO CLINICAL PRACTICE: The implementation of a back massage shows positive improvements in the sleep quality of ICU patients. The training and theory of massage interventions should be further applied when developing courses in critical care nursing.

Investigation of the bindings of a class of inhibitors with GSK3ß kinase using thermodynamic integration MD simulation and kinase assay.

GSK3ß kinase is a noteworthy target for discovery of the drugs that will be used to treat several diseases. In the effort to identify a new inhibitor lead compound, we utilized thermodynamic integration (TI)-molecular dynamics (MD) simulation and kinase assay to investigate the bindings between GSK3ß kinase and five compounds that were analogous to a known inhibitor with an available crystal structure. TI-MD simulations of the first two compounds (analogs 1 and 2) were used for calibration. The computed binding affinities of analogs 1 and 2 agreed well with the experimental results. The rest three compounds (analogs 3-5) were newly obtained from a database search, and their affinity data were newly measured in our labs. TI-MD simulations predicted the binding modes and the computed ΔΔG values have a reasonably good correlation with the experimental affinity data. These newly identified inhibitors appear to be new leads according to our survey of GSK3ß inhibitors listed in recent review articles. The predicted binding modes of these compounds should aid in designing new derivatives of these compounds in the future.

Investigation of differences in the binding affinities of two analogous ligands for untagged and tagged p38 kinase using thermodynamic integration MD simulation.

Thermodynamic integration (TI) molecular dynamics (MD) simulations for the binding of a pair of a reference ("ref") ligand and an analogous ("analog") ligand to either tagged (with six extra residues at the N-terminus) or untagged p38 kinase proteins were carried out in order to probe how the binding affinity is influenced by the presence or absence of the peptide tag in p38 kinase. This possible effect of protein length on the binding affinity of a ligand-which is seldom addressed in the literature-is important because, even when two labs claim to have performed experiments with the same protein, they may actually have studied variants of the same protein with different lengths because they applied different protein expression conditions/procedures. Thus, if we wanted to compare ligand binding affinities measured in the two labs, it would be necessary to account for any variation in ligand binding affinity with protein length. The pair of ligand-p38 kinase complexes examined in this work (pdb codes: 3d7z and 3lhj, respectively) were ideal for investigating this effect. The experimentally determined binding energy for the ref ligand with the untagged p38 kinase was -10.9 kcal mol(-1), while that for the analog ligand with the tagged p38 kinase was -11.9 kcal mol(-1). The present TI-MD simulation of the mutation of the ref ligand into the analog ligand while the ligand is bound to the untagged p38 kinase predicted that the binding affinity of the analog ligand is 2.0 kcal mol(-1) greater than that of the ref ligand. A similar simulation also indicated that the same was true for ligand binding to the tagged protein, but in this case the binding affinity for the analog ligand is 2.5 kcal mol(-1) larger than that for the ref ligand. These results therefore suggest that the presence of the peptide tag on p38 kinase increased the difference in the binding energies of the ligands by a small amount of 0.5 kcal mol(-1). This result supports the assumption that the presence of a peptide tag has only a minor effect on ΔG values. The error bars in the computed ΔG values were then estimated via confidence interval analysis and a time autocorrelation function for the quantity dV/dλ. The estimated correlation time was ~0.5 ps and the error bar in the ΔG values estimated using nanosecond-scale simulations was ±0.3 kcal mol(-1) at a confidence level of 95%. These predicted results can be verified in future experiments and should prove useful in subsequent similar studies. Graphical Abstract Thermodynamic cycles for binding of two analogous ligands with untagged and tagged p38 kinases and associated Gibbs free energy.

Acute pesticide poisoning outcomes: a nationwide study in Taiwan.

BACKGROUND: This study presents the findings of a nationwide study of acute pesticide poisoning (APP) outcomes, including outcome predictors such as physician and hospital volume and associated factors. METHODS: This study of data contained in the Taiwan National Health Insurance Research Database analysed 27 046 patients who had been hospitalised for APP from January 1996 to December 2007. Patient characteristics were then compared among quartiles. The primary outcome measures were length of stay (LOS) and hospital treatment cost. Effect size (ES) was compared among three equally divided periods, and multiple regression models were used to identify outcome predictors. RESULTS: The overall prevalence of APP per 100 000 patients decreased from 12.43 in 1996 to 6.87 in 2007. The LOS for APP treatment was negatively associated with physician volume during the study period. Both LOS and hospital treatment cost were lowest in the high hospital volume subgroup. Comparisons of LOS and hospital treatment cost among the three periods showed that high-volume hospitals and high-volume physicians had better ESs compared to low-volume hospitals and low-volume physicians. Age and number of co-morbidities had significant positive associations with LOS, while admission year, male gender, hospital level, hospital volume and physician volume had significant negative associations with LOS (p<0.05). Hospital treatment cost and hospital level correlated positively with admission year, number of co-morbidities and LOS but correlated negatively with hospital volume and physician volume (p<0.05). CONCLUSIONS: In APP patients, treatment by a high-volume physician can reduce LOS and treatment cost.

Using thermodynamic integration MD simulation to compute relative protein-ligand binding free energy of a GSK3ß kinase inhibitor and its analogs.

Thermodynamic integration molecular dynamics simulation was used to investigate how TI-MD simulation preforms in reproducing relative protein-ligand binding free energy of a pair of analogous GSK3ß kinase inhibitors of available experimental data (see Fig. 1), and to predict the affinity for other analogs. The computation for the pair gave a ΔΔG of 1.0 kcal/mol, which was in reasonably good agreement with the experimental value of -0.1 kcal/mol. The error bar was estimated at 0.5 kcal/mol. Subsequently, we employed the same protocol to proceed with simulations to find analogous inhibitors with a stronger affinity. Four analogs with a substitution at one site inside the binding pocket were the first to be tried, but no significant enhancement in affinity was found. Subsequent simulations for another 7 analogs was focused on substitutions at the benzene ring of another site, which gave two analogs (analogs 9 and 10) with ΔΔG values of -0.6 and -0.8 kcal/mol, respectively. Both analogs had a OH group at the meta position and another OH group at the ortho position at the other side of the benzene ring, as shown in Table 3. To explore further, another 4 analogs with this characteristic were investigated. Three analogs with ΔΔG values of -2.2, -1.7 and -1.2 kcal/mol, respectively, were found. Hydrogen bond analysis suggested that the additional hydrogen bonds of the added OH groups with Gln185 and/or Asn64, which did not appear in the reference inhibitor or as an analog with one substitution only in the examined cases, were the main contributors to an enhanced affinity. A prediction for better inhibitors should interest experimentalists of enzyme and/or cell assays. Analysis of the interactions between GSK3ß kinase and the investigated analogs will be useful in the design of GSK3ß kinase inhibitors for compounds of this class.

Acute quadriparesis caused by spinal arteriovenous malformation: a case report.

Arteriovenous malformations (AVMs) in the spinal cord are relatively rare lesions, especially in the cervical region. Here we report a case of cervical spinal AVM with hemorrhage in a young man who developed acute quadriparesis during exercise. For spinal AVM, emergent spinal magnetic resonance imaging (MRI) is a useful screening tool, and angiography can provide the most important diagnostic information. The emergency physician should have a high index of suspicion for diagnosis and appropriate management of this rare condition. Early diagnosis and management is essential to preserve neurologic functioning.

Correlation between dissociation and catalysis of SARS-CoV main protease.

The dimeric interface of severe acute respiratory syndrome coronavirus main protease is a potential target for the anti-SARS drug development. We have generated C-terminal truncated mutants by serial truncations. The quaternary structure of the enzyme was analyzed using both sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation. Global analysis of the combined results showed that truncation of C-terminus from 306 to 300 had no appreciable effect on the quaternary structure, and the enzyme remained catalytically active. However, further deletion of Gln-299 or Arg-298 drastically decreased the enzyme activity to 1-2% of wild type (WT), and the major form was a monomeric one. Detailed analysis of the point mutants of these two amino acid residues and their nearby hydrogen bond partner Ser-123 and Ser-139 revealed a strong correlation between the enzyme activity loss and dimer dissociation.

[Evaluation of the reliability and validity of the Chinese version of the confusion assessment method for the intensive care unit].

This study was designed to evaluate the reliability and validity of the Chinese version of the diagnostic and statistical manual (DSM) of mental disorders written by Ely et al as a confusion assessment method for the intensive care unit (CAM-ICU) for diagnosing delirium. Purposive sampling was used to recruit 31 patients in a southern medical center ICU. Data were collected by two interviewers who used CAM-ICU to test inter-rater consistency. DSM served as the delirium diagnosis standard to test CAM-ICU validity and calculate sensitivity and specificity. The inter-rater reliability Kappa value for CAM-ICU applied to delirium diagnosis was .48 (p< .01). The validity PABAK value was .48 (p< .01) and McNemar's test value was p = .72. The sensitivity achieved by the two interviewers was 89%, versus 96% for the doctor. The CAM-ICU is a method that helps ICU nursing staff to detect occurrences of delirium rapidly and easily, permitting early intervention treatment with fewer complications.

DYT1 mutation in a cohort of Taiwanese primary dystonias.

To investigate the DYT1 gene mutation in Chinese ethnic, we examined a series of 200 patients with primary dystonias (11 familial and 189 sporadic), 53 of their asymptomatic relatives, 97 patients with familial or early-onset parkinsonism, and 200 healthy subjects. The GAG deletion at codon 946 was only found in three sporadic dystonia patients and seven of their asymptomatic familial members. The frequency of GAG deletion was 1.5% in dystonia patients, and was 6.7% in early-onset dystonias (< or = 26 years). We conclude that DYT1 mutation is a minor cause of primary dystonias in a cohort of Taiwanese population.

Critical assessment of important regions in the subunit association and catalytic action of the severe acute respiratory syndrome coronavirus main protease.

The severe acute respiratory syndrome (SARS) coronavirus (CoV) main protease represents an attractive target for the development of novel anti-SARS agents. The tertiary structure of the protease consists of two distinct folds. One is the N-terminal chymotrypsin-like fold that consists of two structural domains and constitutes the catalytic machinery; the other is the C-terminal helical domain, which has an unclear function and is not found in other RNA virus main proteases. To understand the functional roles of the two structural parts of the SARS-CoV main protease, we generated the full-length of this enzyme as well as several terminally truncated forms, different from each other only by the number of amino acid residues at the C- or N-terminal regions. The quaternary structure and K(d) value of the protease were analyzed by analytical ultracentrifugation. The results showed that the N-terminal 1-3 amino acid-truncated protease maintains 76% of enzyme activity and that the major form is a dimer, as in the wild type. However, the amino acids 1-4-truncated protease showed the major form to be a monomer and had little enzyme activity. As a result, the fourth amino acid seemed to have a powerful effect on the quaternary structure and activity of this protease. The last C-terminal helically truncated protease also exhibited a greater tendency to form monomer and showed little activity. We concluded that both the C- and the N-terminal regions influence the dimerization and enzyme activity of the SARS-CoV main protease.

Quaternary structure of the severe acute respiratory syndrome (SARS) coronavirus main protease.

SARS (severe acute respiratory syndrome) has been one of the most severe viral infectious diseases last year and still remains as a highly risky public health problem around the world. Exploring the types of interactions responsible for structural stabilities of its component protein molecules constitutes one of the approaches to find a destabilization method for the virion particle. In this study, we performed a series of experiments to characterize the quaternary structure of the dimeric coronavirus main protease (M(pro), 3CL(pro)). By using the analytical ultracentrifuge, we demonstrated that the dimeric SARS coronavirus main protease exists as the major form in solution at protein concentration as low as 0.10 mg/mL at neutral pH. The enzyme started to dissociate at acidic and alkali pH values. Ionic strength has profound effect on the dimer stability indicating that the major force involved in the subunit association is ionic interactions. The effect of ionic strength on the protease molecule was reflected by the drastic change of electrostatic potential contour of the enzyme in the presence of NaCl. Analysis of the crystal structures indicated that the interfacial ionic interaction was attributed to the Arg-4...Glu-290 ion pair between the subunits. Detailed examination of the dimer-monomer equilibrium at different pH values reveals apparent pK(a) values of 8.0 +/- 0.2 and 5.0 +/- 0.1 for the Arg-4 and Glu-290, respectively. Mutation at these two positions reduces the association affinity between subunits, and the Glu-290 mutants had diminished enzyme activity. This information is useful in searching for substances that can intervene in the subunit association, which is attractive as a target to neutralize the virulence of SARS coronavirus.

Dual functional roles of ATP in the human mitochondrial malic enzyme.

Human mitochondrial malic enzyme is a regulatory enzyme with ATP as an inhibitor. Structural studies reveal that the enzyme has two ATP-binding sites, one at the NAD(+)-binding site in the active center and the other at the exo site in the tetramer interface. Inhibition of the enzyme activity is due to the competition between ATP and NAD(+) for the nucleotide-binding site at the active center with an inhibition constant of 81 microM. Binding of the ATP molecule at the exo site, on the other hand, is important for the maintenance of the quaternary structural integrity. The enzyme exists in solution at neutral pH and at equilibrium of the dimer and tetramer with a dissociation constant (K(TD)) of 0.67 microM. ATP, at a physiological concentration, shifts the equilibrium toward tetramer and decreases the K(TD) by many orders of magnitude. Mutation of a single residue Arg542 at the tetrameric interfacial exo site resulted in dimeric mutants. ATP thus has dual functional roles in the mitochondrial malic enzyme.

Antrodia camphorata polysaccharides exhibit anti-hepatitis B virus effects.

Polysaccharides were extracted from fruiting bodies and cultured mycelia from five Antrodia camphorata strains. Polysaccharide profiles of the five strains, as determined by high-performance anion-exchange chromatography, showed varying yields and composition of neutral sugars. A. camphorata fruiting bodies also had different polysaccharide patterns compared to the cultured mycelium. Analysis of 26-day-old mycelia showed that the neutral sugars galactose, glucose, mannose, and galactosamine were predominant. All mycelia polysaccharide preparations exhibited anti-hepatitis B virus activity. Polysaccharides from strain B86 at a concentration of 50 microg ml(-1) showed the highest level of anti-hepatitis B surface antigen effect, which was higher than alpha-interferon at a dosage of 1000 U ml(-1). Only strains B86 and 35398 had substantial anti-hepatitis B e antigen activities. None of the polysaccharides exhibited cytotoxic effects.