Inhibition of dengue viruses by N-methylcytisine thio derivatives through targeting viral envelope protein and NS2B-NS3 protease.

Dengue virus (DENV) is a significant global health threat, causing millions of cases worldwide each year. Developing antiviral drugs for DENV has been a challenging endeavor. Our previous study identified anti-DENV properties of two (-)-cytisine derivatives contained substitutions within the 2-pyridone core from a pool of 19 (-)-cytisine derivatives. This study aimed to expand on the previous research by investigating the antiviral potential of N-methylcytisine thio (mCy thio) derivatives against DENV, understanding the molecular mechanisms of antiviral activity for the active thio derivatives. The inhibitory assays on DENV-2-induced cytopathic effect and infectivity revealed that mCy thio derivatives 3 ((1R,5S)-3-methyl-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocine-8-thione) and 6 ((1S,5R)-3-methyl-2-thioxo-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one) were identified as the active compounds against both DENV-1 and DENV-2. Derivative 6 displayed robust antiviral activity against DENV-2, with EC50 values ranging from 0.002 to 0.005 µM in different cell lines. Derivative 3 also exhibited significant antiviral activity against DENV-2. The study found that these compounds are effective at inhibiting DENV-2 at both the entry stage (including virus attachment) and post-entry stages of the viral life cycle. The study also investigated the inhibition of the DENV-2 NS2B-NS3 protease activity by these compounds. Derivative 6 demonstrated notably stronger inhibition compared to mCy thio 3, revealing its dual antiviral action at both the entry and post-entry stages. Molecular docking simulations indicated that mCy thio derivatives 3 and 6 bind to the domain I and III of the DENV E protein, as well as the active of NS2B-NS3 protease, suggesting their molecular interactions with the virus. The study demonstrates the antiviral efficacy of N-methylcytisine thio derivatives against DENV. It provides valuable insights into the potential interactions between these compounds and viral target proteins, which could be useful in the development of antiviral drugs for DENV.

Discovery of Novel Spike Inhibitors against SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current coronavirus disease pandemic. With the rapid evolution of variant strains, finding effective spike protein inhibitors is a logical and critical priority. Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV-2 viral entry, and thus related therapeutic approaches associated with the spike protein-ACE2 interaction show a high degree of feasibility for inhibiting viral infection. Our computer-aided drug design (CADD) method meticulously analyzed more than 260,000 compound records from the United States National Cancer Institute (NCI) database, to identify potential spike inhibitors. The spike protein receptor-binding domain (RBD) was chosen as the target protein for our virtual screening process. In cell-based validation, SARS-CoV-2 pseudovirus carrying a reporter gene was utilized to screen for effective compounds. Ultimately, compounds C2, C8, and C10 demonstrated significant antiviral activity against SARS-CoV-2, with estimated EC50 values of 8.8 µM, 6.7 µM, and 7.6 µM, respectively. Using the above compounds as templates, ten derivatives were generated and robust bioassay results revealed that C8.2 (EC50 = 5.9 µM) exhibited the strongest antiviral efficacy. Compounds C8.2 also displayed inhibitory activity against the Omicron variant, with an EC50 of 9.3 µM. Thus, the CADD method successfully discovered lead compounds binding to the spike protein RBD that are capable of inhibiting viral infection.

Dual Effects of 3-epi-betulin from Daphniphyllum glaucescens in Suppressing SARS-CoV-2-Induced Inflammation and Inhibiting Virus Entry.

The continuous emergence of SARS-CoV-2 variants has led to a protracted global COVID-19 pandemic with significant impacts on public health and global economy. While there are currently available SARS-CoV-2 vaccines and therapeutics, most of the FDA-approved antiviral agents directly target viral proteins. However, inflammation is the initial immune pathogenesis induced by SARS-CoV-2 infection, there is still a need to find additional agents that can control the virus in the early stages of infection to alleviate disease progression for the next pandemic. Here, we find that both the spike protein and its receptor CD147 are crucial for inducing inflammation by SARS-CoV-2 in THP-1 monocytic cells. Moreover, we find that 3-epi-betulin, isolated from Daphniphyllum glaucescens, reduces the level of proinflammatory cytokines induced by SARS-CoV-2, consequently resulting in a decreased viral RNA accumulation and plaque formation. In addition, 3-epi-betulin displays a broad-spectrum inhibition of entry of SARS-CoV-2 pseudoviruses, including Alpha (B.1.1.7), Eplison (B.1.429), Gamma (P1), Delta (B.1.617.2) and Omicron (BA.1). Moreover, 3-epi-betulin potently inhibits SARS-CoV-2 infection with an EC50 of <20 µM in Calu-3 lung epithelial cells. Bioinformatic analysis reveals the chemical interaction between the 3-epi-betulin and the spike protein, along with the critical amino acid residues in the spike protein that contribute to the inhibitory activity of 3-epi-betulin against virus entry. Taken together, our results suggest that 3-epi-betulin exhibits dual effect: it reduces SARS-CoV-2-induced inflammation and inhibits virus entry, positioning it as a potential antiviral agent against SARS-CoV-2.

Recognition of a Novel Gene Signature for Human Glioblastoma.

Glioblastoma (GBM) is one of the most common malignant and incurable brain tumors. The identification of a gene signature for GBM may be helpful for its diagnosis, treatment, prediction of prognosis and even the development of treatments. In this study, we used the GSE108474 database to perform GSEA and machine learning analysis, and identified a 33-gene signature of GBM by examining astrocytoma or non-GBM glioma differential gene expression. The 33 identified signature genes included the overexpressed genes COL6A2, ABCC3, COL8A1, FAM20A, ADM, CTHRC1, PDPN, IBSP, MIR210HG, GPX8, MYL9 and PDLIM4, as well as the underexpressed genes CHST9, CSDC2, ENHO, FERMT1, IGFN1, LINC00836, MGAT4C, SHANK2 and VIPR2. Protein functional analysis by CELLO2GO implied that these signature genes might be involved in regulating various aspects of biological function, including anatomical structure development, cell proliferation and adhesion, signaling transduction and many of the genes were annotated in response to stress. Of these 33 signature genes, 23 have previously been reported to be functionally correlated with GBM; the roles of the remaining 10 genes in glioma development remain unknown. Our results were the first to reveal that GBM exhibited the overexpressed GPX8 gene and underexpressed signature genes including CHST9, CSDC2, ENHO, FERMT1, IGFN1, LINC00836, MGAT4C and SHANK2, which might play crucial roles in the tumorigenesis of different gliomas.

One-Year Treatment Outcome of Profile Changes After Transcutaneous Maxillary Distraction Osteogenesis in Growing Children With Cleft Lip and Palate.

OBJECTIVE: To evaluate the long-term stability of LeFort I osteotomy followed by distraction osteogenesis with a transcutaneous rigid external device for the treatment of severe maxillary hypoplasia in patients with cleft lip and palate. PATIENTS AND METHODS: Nine patients with cleft lip and palate underwent rigid external distraction after a LeFort I osteotomy for maxillary advancement. Lateral cephalometric films were analyzed for assessment of treatment outcome and stability in 1 month, 6 months, and 1 year after distraction. RESULTS: Significant maxillary advancement was observed in the horizontal direction, with the anterior nasal spine (ANS) distance of the maxilla increasing by an average of 20.5 ± 5.1 mm after distraction. The ANS relapse rates in 6 months and 1 year were 8.7% and 12.8%, respectively. The mean inclination of upper incisors to the palatal plane was almost unchanged (before: 109.8° ± 6.6°; after: 108.9° ± 7.5°). The movement ratios at the nasal tip/ANS, soft tissue A point/A point, and the upper vermilion border/upper incisor edge were 0.36:1, 0.72:1, and 0.83:1, respectively. CONCLUSION: Considerable maxillary advancement was achieved with less change of incisors inclination after distraction. Moreover, the relapse rate after 1 year was minimal. The concave facial profile was improved as well as the facial balance and aesthetics.

The Feasibility of a Machine Learning Approach in Predicting Successful Ventilator Mode Shifting for Adult Patients in the Medical Intensive Care Unit.

Background and Objectives: Traditional assessment of the readiness for the weaning from the mechanical ventilator (MV) needs respiratory parameters in a spontaneous breath. Exempted from the MV disconnecting and manual measurements of weaning parameters, a prediction model based on parameters from MV and electronic medical records (EMRs) may help the assessment before spontaneous breath trials. The study aimed to develop prediction models using machine learning techniques with parameters from the ventilator and EMRs for predicting successful ventilator mode shifting in the medical intensive care unit. Materials and Methods: A retrospective analysis of 1483 adult patients with mechanical ventilators for acute respiratory failure in three medical intensive care units between April 2015 and October 2017 was conducted by machine learning techniques to establish the predicting models. The input candidate parameters included ventilator setting and measurements, patients' demographics, arterial blood gas, laboratory results, and vital signs. Several classification algorithms were evaluated to fit the models, including Lasso Regression, Ridge Regression, Elastic Net, Random Forest, Extreme Gradient Boosting (XGBoost), Support Vector Machine, and Artificial Neural Network according to the area under the Receiver Operating Characteristic curves (AUROC). Results: Two models were built to predict the success shifting from full to partial support ventilation (WPMV model) or from partial support to the T-piece trial (sSBT model). In total, 3 MV and 13 nonpulmonary features were selected for the WPMV model with the XGBoost algorithm. The sSBT model was built with 8 MV and 4 nonpulmonary features with the Random Forest algorithm. The AUROC of the WPMV model and sSBT model were 0.76 and 0.79, respectively. Conclusions: The weaning predictions using machine learning and parameters from MV and EMRs have acceptable performance. Without manual measurements, a decision-making system would be feasible for the continuous prediction of mode shifting when the novel models process real-time data from MV and EMRs.

Time-Evolved SERS Signatures of DEP-Trapped Aß and Zn2+Aß Peptides Revealed by a Sub-10 nm Electrode Nanogap.

Alzheimer's disease (AD) has become highly relevant in aging societies, yet the fundamental molecular basis for AD is still poorly understood. New tools to study the undergoing structural conformation changes of amyloid beta (Aß) peptides, the pathogenic hallmark of AD, could play a crucial role in the understanding of the underlying mechanisms of misfolding and cytotoxicity of this peptide. It has been recently reported that Zn2+ interacts with Aß and changes its aggregation pathway away from less harmful fibrillar forms to more toxic species. Here, we present a versatile platform based on a set of sub-10 nm nanogap electrodes for the manipulation and sensing of biomolecules in the physiological condition at a low copy number, where molecules are trapped via dielectrophoresis (DEP) across the nanogap, which also serves as a surface-enhanced Raman spectroscopy hotspot. In this study, we demonstrate that our electrode nanogap platform can be used to study the structural difference between Aß40 and ZnAß40 peptides at different aggregation stages in the physiologically relevant concentration and in solution phase. The Raman spectroscopic signatures of the DEP-captured neuropeptides prove the device to be attractive as a label-free bioanalytical tool.

Effects of Dissolved Gases on the Amyloid Fibril Morphology.

The onset or progression of numerous neurodegenerative diseases occurs due to aggregation of proteins that ultimately form fibrils. The assembly and morphology of fibrils are susceptible to environmental factors. In this work, we used atomic force microscopy (AFM) to investigate the effects of dissolved nitrogen and oxygen molecules on the morphology of fibrils formed by a hydrophobic amyloid peptide implicated in amyotrophic lateral sclerosis, 15 repeats of glycine-alanine, on a highly oriented pyrolytic graphite substrate. We started with preformed fibril solutions that were then diluted with buffers of different gas conditions, resulting in the aggregation of the fibrils into different morphologies that were revealed by AFM after adsorption on the substrate. Straight fibrils were observed in both degassed and ambient buffers, but a stronger lateral association was seen in degassed buffers. Smaller and softer fibrils were observed in O2-supersaturated buffers, and plaque-like fibril aggregates of considerably large size were evident in N2-supersaturated buffers. In overnight incubation experiments, we observed changes in both the morphology and height of the fibril aggregates, and their evolution varied with different gas conditions. These findings indicate that the gas type and concentration affect the aggregation of amyloid fibrils and may facilitate the development of biomaterial applications and treatments for amyloid-related diseases.

Accuracy assessment of computer-aided three-dimensional simulation and navigation in orthognathic surgery (CASNOS).

PURPOSE: This study is aimed for measuring the accuracy of simulation and prediction of our CASNOS protocol in adult patients treated with 2-jaw orthognathic surgery. METHODS: Adult patients with skeletal Class III malocclusions requiring 2-jaw orthognathic surgery were enrolled in the study. Three-dimensional imaging data of 1-month pre-surgical (T1) and 6-month post-surgical (T2) CT were compared to assess accuracy of CASNOS planning. The accuracy of CASNOS protocol was evaluated by calculating the differences in the positions of selected landmarks between simulated surgical and post-surgical 3D images parameters, including ANB, A-Nv, Pog-Nv, and the positions of selected landmarks (ANS, Point A, Point B, Pog) changes in horizontal (x-axis) and vertical (y-axis) directions. Overall geographical discrepancy of planning was assessed by superimposing the color mapping of T1 and T2 imaging. RESULTS: Thirty adult patients with a mean age of 20.6 ± 1.5 years (female/male = 18/12) were enrolled. The geographical changes of overall superimposition between the planned and post-surgical imaging was 0.60 ± 0.19 mm (range: 0.42-1.08 mm). The discrepancies between simulated and post-surgical ANB, A-Nv, Pog-Nv were 1.16 ± 0.36°, 1.25 ± 0.33 mm, 1.19 ± 0.35 mm, respectively. The deviations between simulated and post-surgical Point A and Point B positions were within 1 mm in horizontal and vertical directions. CONCLUSION: The application of the pre-designed bony guiding splints of CASNOS protocol can allow surgeons to treat patients with craniofacial deformities precisely. CASNOS provides a novel approach for orthodontists and surgeons accurately remedying the patients with complex craniofacial discrepancies.

The Effect of Fatigue on Leg Muscle Activation and Tibial Acceleration During a Jumping Task.

CONTEXT: Lower-extremity stress fractures (SFx) are a common occurrence during load-bearing activities of jumping and landing. To detect biomechanical changes during jumping postinjury, a fatigue model could be used. OBJECTIVE: To evaluate muscle activation in the lower leg and tibial accelerations (TAs) prefatigue to postfatigue following a jumping task in those with and without a history of SFx. DESIGN: Repeated-measures. SETTING: Athletic Training Research Lab. PARTICIPANTS: A total of 30 active college-aged students with and without a history of lower-extremity (leg or foot) SFx (15 males and 15 females; 21.5 [5.04] y, height = 173.5 [12.7] cm, weight = 72.65 [16.4] kg). INTERVENTION: A maximal vertical jump on one leg 3 times with arms folded across the chest prefatigue to postfatigue was performed. Fatigue protocol was standing heel raises on a custom-built platform at a pace controlled by a metronome until task failure was reached. Legs were tested using a randomized testing order. Electromyographic (EMG) surface electrodes were placed on the medial gastrocnemius, soleus, and tibialis anterior following a standardized placement protocol. A triaxial accelerometer was attached to the proximal anteromedial surface of the tibia. MAIN OUTCOME MEASURES: Linear envelopes of the medial gastrocnemius, soleus, and tibialis anterior and peak accelerations (resultant acceleration takeoff and landing). RESULTS: Significant interaction for leg × test for tibialis anterior with a posttest difference between SFx and control (P = .05). There were decreases in EMG linear envelope following fatigue for medial gastrocnemius (P < .01) and tibialis anterior (P = .12) pretest to posttest. At takeoff, TA was greater in the SFx contralateral leg in comparison with the control leg (P = .04). At landing, TA was greater in posttest (P < .01) and in the SFx leg compared with SFx contralateral (P = .14). CONCLUSION: A decrease in muscle activity and an increase in TA following fatigue were noted for all subjects but especially for those with a history of SFx.

Blood loss and operative time associated with orthognathic surgery utilizing a novel navigation system in cleft lip and palate patients.

PURPOSE: This retrospective study evaluated the volume of blood loss and operative time associated with management of nongrowing patients with cleft lip and palate (CLP) using bimaxillary orthognathic surgery (OGS) designed by a three-dimensional (3D) computer-assisted simulation and navigation for orthognathic surgery (CASNOS) system. METHODS: This study included 53 skeletal Class III nongrowing patients with unilateral CLP who underwent bimaxillary OGS using either the CASNOS protocol (n = 30) or the traditional two-dimensional (2D) method (n = 23). The skeletal parameters of jaw-bone components, the levels of hemoglobin (Hb) and hematocrit (Hct) were measured before and after surgery. The estimated blood loss and actual blood loss (ABL) were also calculated. RESULTS: The two groups did not differ significantly with regard to the demographic parameters (age, gender, and body mass index), the preoperative skeletal parameters and surgical changes of jaw-bone components. The mean ABL of the CASNOS group was significantly lower than that of the control group (915.6 ± 280.5 vs. 1204.9 ± 201.0 ml, p < 0.001), and the changes in Hb and Hct level also followed a similar pattern in both groups. The mean operative time was significantly shorter in the CASNOS group compared with the control group (384.2 ± 48.5 vs. 469.0 ± 94.9 min, p < 0.001). CONCLUSION: This study demonstrated that the application of the 3D CASNOS approach in OGS for the management of complicated Class III nongrowing patients with CLP significantly shortened the operative time and reduced ABL in comparison with the traditional 2D methods.

Concordance between different trophectoderm biopsy sites and the inner cell mass of chromosomal composition measured with a next-generation sequencing platform.

STUDY QUESTION: In PGS, does chromosomal constitution differ among trophectoderm (TE) biopsy sites and between them and the inner cell mass (ICM)? SUMMARY ANSWER: The ploidy concordance between ICM and TE was independent of whether the biopsy site in the TE was near to or far from the ICM. WHAT IS KNOWN ALREADY: TE biopsies are considered less harmful to developing embryos than blastomere biopsies. Removal of multi-cellular samples permits high-resolution next-generation sequencing (Veriseq NGS) to detect aneuploidy present in a minority of cells (mosaicism of diploid and aneuploid cells). However, the prevalence of ploidy discrepancies between different TE biopsy sites and the ICM, as well as confined mosaicism (aneuploidy only in a particular area), has not been established. STUDY DESIGN, SIZE, DURATION: Biopsies were taken from a site opposite to the ICM (TE1), near the ICM (TE2) and within the ICM of the same embryo in 33 donated blastocysts obtained from 12 volunteer patients. The samples were analyzed by the Veriseq NGS to assess ploidy concordance. PARTICIPANTS/MATERIALS, SETTING, METHODS: The mean age of the patients was 34.4 years, and samples from all three biopsy sites were achieved in 29 frozen thawed blastocysts. The aneuploid percentage in each sample was interpreted by Veriseq NGS at the finest resolution involving the number of reads after filtering, sample overall noise score, and average quality/alignment scores according to the Veriseq quality control assessment. Ploidy concordance was then assessed between different TE fractions, and between the TE and ICM. MAIN RESULTS AND THE ROLE OF CHANCE: The euploid rates were similar in the TEs and ICM, and no preferential allocation of euploid lineage within a blastocyst was demonstrated. Whether the biopsy site in the TE was near to or far from the ICM, the chromosomal consistency rate was similar [TE1-to-ICM, 86.2% (25/29) versus TE2-to-ICM, 89.7% (26/29); P = 1.0], suggesting that the cells with different chromosomal components may spread randomly throughout the TE. The following two types of inconsistent PGS conclusions between TE and ICM due to confined mosaicism were observed: (i) euploid TE with mosaic ICM (3%) (1/29); and (ii) mosaic TE with euploid ICM (3%) (1/29) or with aneuploid ICM (7%) (2/29). Thus, the overall rate of confined mosaicism was 14% (4/29). LARGE SCALE DATA: N/A. LIMITATION, REASONS FOR CAUTION: The approach used in the present study was affected by biopsy manipulation limitations involving possible cell contamination and the technical challenge of comprehensive chromosomal screening (CCS) procedures. WIDER IMPLICATIONS OF THE FINDINGS: The rate of confined mosaicism in the blastocysts was estimated in this preliminary study, thus, specifying the incidence of biological sampling biases. The results also verified the random distribution of different cell lineages, and the representative value of a single biopsied sample from the TE. STUDY FUNDING AND CONFLICT OF INTEREST(S): No external funding was obtained; all the authors declare no conflicts of interest regarding this study.

Optical characterization of porcine articular cartilage using a polarimetry technique with differential Mueller matrix formulism.

A method is proposed for characterizing the optical properties of articular cartilage sliced from a pig's thighbone using a Stokes-Mueller polarimetry technique. The principal axis angle, phase retardance, optical rotation angle, circular diattenuation, diattenuation axis angle, linear diattenuation, and depolarization index properties of the cartilage sample are all decoupled in the proposed analytical model. Consequently, the accuracy and robustness of the extracted results are improved. The glucose concentration, collagen distribution, and scattering properties of samples from various depths of the articular cartilage are systematically explored via an inspection of the related parameters. The results show that the glucose concentration and scattering effect are both enhanced in the superficial region of the cartilage. By contrast, the collagen density increases with an increasing sample depth.

Use of Nasal Conformer After Birth Effectively Improves Nostril Symmetry in Patients With Unilateral Incomplete Cleft Lip.

PURPOSE: To investigate the clinical effects of preoperative nasoalveolar molding (NAM) and nasal conformer use in patients with unilateral incomplete cleft lip on the basis of their medical records and images. PATIENTS AND METHODS: Data and images of 16 patients born with unilateral incomplete cleft lip who were hospitalized between January 2015 and August 2017 were retrieved from the medical records. The primary outcome was the extent of improvement in columella height (CH) before cheiloplasty. Other outcome measurements included the CH, nostril width, and nostril height, which were measured by ImageJ image processing software (version 1.4; National Institutes of Health, Bethesda, MD) and presented as ratios. Mann-Whitney U tests were used to compare the non-normally distributed data. RESULTS: Patients in the NAM group and those in the nasal conformer group showed significantly improved (P < .05) preoperative cleft-side CH-to-normal-side CH ratios compared with the corresponding ratios at birth. There was no significant difference in terms of the extent of improvement in CH between the groups. CONCLUSIONS: Preoperative use of nasal conformers in patients with unilateral incomplete cleft lip not only corrects the deformed nasal cartilage but also increases the CH and improves the overall preoperative nasal symmetry. In addition, compared with NAM, this method costs less, is more straightforward, and requires fewer outpatient clinic visits.

The Glycine-Alanine Dipeptide Repeat from C9orf72 Hexanucleotide Expansions Forms Toxic Amyloids Possessing Cell-to-Cell Transmission Properties.

Hexanucleotide expansions, GGGGCC, in the non-coding regions of the C9orf72 gene were found in major frontotemporal lobar dementia and amyotrophic lateral sclerosis patients (C9FTD/ALS). In addition to possible RNA toxicity, several dipeptide repeats (DPRs) are translated through repeat-associated non-ATG-initiated translation. The DPRs, including poly(GA), poly(GR), poly(GP), poly(PR), and poly(PA), were found in the brains and spinal cords of C9FTD/ALS patients. Among the DPRs, poly(GA) is highly susceptible to form cytoplasmic inclusions, which is a characteristic of C9FTD/ALS. To elucidate DPR aggregation, we used synthetic (GA)15 DPR as a model system to examine the aggregation and structural properties in vitro. We found that (GA)15 with 15 repeats fibrillates rapidly and ultimately forms flat, ribbon-type fibrils evidenced by transmission electron microscopy and atomic force microscopy. The fibrils are capable of amyloid dye binding and contain a characteristic cross-ß sheet structure, as revealed by x-ray scattering. Furthermore, using neuroblastoma cells, we demonstrated the neurotoxicity and cell-to-cell transmission property of (GA)15 DPR. Overall, our results show the structural and toxicity properties of GA DPR to facilitate future DPR-related therapeutic development.

Soft Tissue Changes Measured With Three-Dimensional Software Provides New Insights for Surgical Predictions.

PURPOSE: Although computer-aided craniofacial reconstructions allow for simulation of hard tissue changes, the prediction of the final soft tissue facial changes remains a challenge. The purpose of the present study was to evaluate the 3-dimensional (3D) soft tissue changes in patients undergoing 2-jaw orthognathic surgery. PATIENTS AND METHODS: For the present retrospective cohort study, 40 consecutive patients (11 men and 29 women; mean age 23.5 ± 4.9 years) who had undergone 2-jaw orthognathic surgery were selected. We obtained the medical and dental records from 3 weeks before surgery and 6 months after surgery. We used image processing software to segment, superimpose, and quantify the hard and soft tissue displacements in 3 dimensions before and after surgery at 15 paired locations. The soft tissue and hard tissue changes were determined through quantification of homologous landmark displacements between the preoperative and postoperative computed tomography data. We measured the 3D soft and hard tissue changes and the anteroposterior, inferosuperior, and transverse components of the changes. We quantified the ratios between the soft and hard tissue changes, tested Pearson's correlation between these changes, and developed a predictive regression equation for the observations at each location. RESULTS: We found that soft tissue movement followed the hard tissue movement, with a correlation nearly equal to 0.9 (range 0.85 to 0.98), suggesting that in general the soft tissues of the maxillary and mandibular landmarks are affected similarly by the skeletal movements. The anteroposterior component of the soft tissue 3D displacements followed the hard tissue movement with a ratio greater than 0.9 and with high correlation (r > 0.9) in the mandible. CONCLUSION: The results of the present study provide surgeons with a ratio of hard to soft tissue change and the strength of the correlations, which will allow for more accurate 3D predictions for both midline and lateral structures in bimaxillary orthognathic surgical cases. In addition, predictive equations for various landmarks were developed and can be used in computer-based prediction programs to aid in treatment planning of soft tissue changes.

Quantification of VOC emissions from paint spraying on a construction site using solid phase microextraction devices.

The objective of this study was to measure the emission of, and personal exposure to workers, volatile organic compound (VOC) during paint spraying on a construction site. Needle trap samplers (NTSs), which are a green solid phase microextraction sampling technology, were used to obtain air samples at a large music exhibition center. The standard active sampling method using charcoal tubes and a personal air pump, Method 1501, was simultaneously utilized at the sampling sites to assess the workers' VOC exposures. Analysis of the data thus obtained showed that benzene, toluene, ethylenebenzene, and xylenes (BTEXs) were the main emission compounds. Acetone and isobutyl alcohol, which are used as thinning solvents, were detected as minor emission compounds. The emitted concentrations of most compounds were lower than the legal emission limits in Taiwan except that of benzene, for which the 2-ppm time weighted average short-term exposure limit was exceeded. The packed divinylbenzene (DVB) in the NTS was observed under an environmental scanning electron microscope, and many fine aerosols were found to be deposited on the surface of the DVB adsorbents, causing VOC extraction efficiencies after the fifth sampling in the field to decline. Workers on construction sites should be protected from emissions of VOC and fine particulates to preserve their occupational health.

The neuromechanical adaptations to Achilles tendinosis.

KEY POINTS: Achilles tendinosis is a localized degenerative musculoskeletal disorder that develops over a long period of time and leads to a compliant human Achilles tendon. We demonstrate that the compliant Achilles tendon elicited a series of adaptations from different levels of the human movement control system, such as the muscle-tendon interaction, CNS control and other muscles in the lower leg. These results illustrate the human body's capacity to adapt to tendon pathology and provide the physiological basis for intervention or prevention strategies. Human movement is initiated, controlled and executed in a hierarchical system including the nervous system, muscle and tendon. If a component in the loop loses its integrity, the entire system has to adapt to that deficiency. Achilles tendon, when degenerated, exhibits lower stiffness. This local mechanical deficit may be compensated for by an alteration of motor commands from the CNS. These modulations in motor commands from the CNS may lead to altered activation of the agonist, synergist and antagonist muscles. The present study aimed to investigate the effect of tendon degeneration on its mechanical properties, the neuromechanical behaviour of the surrounding musculature and the existence of the CNS modulation accompanying tendinosis. We hypothesize that the degenerated tendon will lead to diminished tissue mechanical properties and protective muscle activation patterns, as well as an up-regulated descending drive from the CNS. Strong evidence, as reported in the present study, indicates that tendinotic tendons are more compliant compared to healthy tendons. This unilateral involvement affected the neuromuscular control on the involved side but not the non-involved side. The muscle-tendon unit on the tendinotic side exhibits a lowered temporal efficiency, which leads to altered CNS control. The altered CNS control is then expressed as an adapted muscle activation pattern in the lower leg. Taken together, the findings of the present study illustrate the co-ordinated multi-level adaptations to a mechanical lesion in a tendon caused by pathology.

Multichannel lens-free CMOS sensors for real-time monitoring of cell growth.

A low-cost platform is proposed for the growth and real-time monitoring of biological cells. The main components of the platform include a PMMA cell culture microchip and a multichannel lens-free CMOS (complementary metal-oxide-semiconductor) / LED imaging system. The PMMA microchip comprises a three-layer structure and is fabricated using a low-cost CO2 laser ablation technique. The CMOS / LED monitoring system is controlled using a self-written LabVIEW program. The platform has overall dimensions of just 130 × 104 × 115 mm(3) and can therefore be placed within a commercial incubator. The feasibility of the proposed system is demonstrated using HepG2 cancer cell samples with concentrations of 5000, 10 000, 20 000, and 40 000 cells/mL. In addition, cell cytotoxicity tests are performed using 8, 16, and 32 mM cyclophosphamide. For all of the experiments, the cell growth is observed over a period of 48 h. The cell growth rate is found to vary in the range of 44∼52% under normal conditions and from 17.4∼34.5% under cyclophosphamide-treated conditions. In general, the results confirm the long-term cell growth and real-time monitoring ability of the proposed system. Moreover, the magnification provided by the lens-free CMOS / LED observation system is around 40× that provided by a traditional microscope. Consequently, the proposed system has significant potential for long-term cell proliferation and cytotoxicity evaluation investigations.

EFFECTS OF L2 LEARNING ORIENTATIONS AND IMPLEMENTATION INTENTIONS ON SELF-REGULATION.

In this study, a classic L2 learning orientation framework and a multi-faceted implementation intention construct were used to predict self-regulation. Attention was particularly paid to the way in which different types of implementation intentions predicted the self-regulatory capacity. A two-phase research design was executed. A pilot was conducted to ensure the reliability and validity of the scales. In the main study, a series of regression analyses examined the links among the variables of interest. The modeling results indicated that the effects of the integrative and instrumental orientations were substantially diminished after the implementation intentions were incorporated into the orientation structure. The empirical findings strongly suggest the need for L2 learners to utilize strategic planning in response to situational and temporal cues in the process of goal pursuit. Further discussions focused on the effects of both orientations and implementation intentions on the self-regulatory capacity in language learning.