EFFECTS OF FUNCTIONAL KNEE BRACES ON NEUROMUSCULAR ADAPTATION IN ANTERIOR CRUCIATE LIGAMENT INJURED PATIENTS

INTRODUCTION: Neuromuscular adaptation in the lower extremity has been found in anterior cruciate ligament (ACL) injured patients, with mechanical and electromyographic alterations such as reduced knee extensor moment and power, increased hamsrings muscle activity, and decreased muscle strength (Berchuck, Andriacchi, Bach, & Reider, 1990; DeVita, Lassiter, Hortobagyi, & Torry, 1998). Functional knee bracing has been a common method to enhance functional knee stability in these patients for the past three decades. However, the long-term effects of knee bracing on ACL-reconstructed (ACL-R) patients have not been reported in the literature. There is thus an urgent need to identify the effects of bracing on the gait displayed by these patients

Primary Cardiac Lymphoma

Primary cardiac lymphoma (PCL) has rarely been reported in Chinese populations. PCL mostly occurs in the right atrium. The clinical manifestations may be variable and are attributed to its location, the presence of congestive heart failure, pericardial effusion, arrhythmia, and cardiomegaly. The prognosis is usually poor because it is usually found too late and therefore, clinicians should be aware of PCL. Imaging examinations are the best methods for initial diagnosis and include echocardiography, computed tomography (CT) scan, magnetic resonance imaging (MRI), and radioisotope scan. However, the final diagnosis is made by pathology, such as cytologic examination of the effusive fluid and tissue biopsy. Because the tumors are difficult to resect, the main treatment for the disease is chemotherapy, which can be successful. Here, we report a 58-year-old man who had a tumor measuring 8 × 5 cm in the right atrium. By clinical staging, including chest X-ray, echocardiography, CT scan of the abdomen, MRI of the heart, whole body tumor Gallium scan, and gastrointestinal series, no metastatic lesion or involvement was found in other parts of the body. Pathologic findings including cytology of pericardial effusion and heart tumor biopsy revealed the case as a diffuse large B-cell lymphoma. After chemotherapy with COP (cyclophosphamide + vincristine + prednisone) and CHOPBE (COP + doxorubicin + bleomycin + etoposide) regimens, the intracardiac tumor had disappeared, but the patient survived for 12 months in total, despite additional radiotherapy over the pericardial lesions. It was presumed that because the tumor was very large and involved all 3 layers of the heart, it did not respond as well to the therapy as expected

Associations between Body Mass Index and serum levels of C-Reactive Protein

Background: Obesity imposes increased risks of cardiovascular disease and glucose intolerance, a phenomenon of chronic inflammation. This study was performed to determine whether higher body mass index (BMI) and central obesity are associated with low-grade inflammation. Methods: 8453 adults aged 20 years and older, were analyzed. Every subject completed a household interview, BMI measurement, serum C-reactive protein (CRP) measurement, and a questionnaire regarding personal health. BMI was divided into quintiles, using multiple linear regression to estimate the relationship between CRP level and BMI quintiles. An extended-model approach was used for covariate adjustment. The association of central obesity and CRP level was examined with this method as well. Results: After controlling for demographics, chronic diseases, health behaviors, and levels of folate and vitamin B12, the β coefficient, representing the change of natural-log-transformed levels of CRP for each 1 kg/m2 increased in BMI, was 0.078(

Establishment of a Knock-In Mouse Model with the SLC26A4 c.919-2A>G Mutation and Characterization of Its Pathology

Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4tm1Dontuh/tm1Dontuh mice) homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4tm1Dontuh/tm1Dontuh mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4tm1Dontuh/tm1Dontuh mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4tm1Dontuh/tm1Dontuh mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4tm1Dontuh/tm1Dontuh mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4−/− mice and Slc26a4loop/loop mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains

3D-partner: a web server to infer interacting partners and binding models

The 3D-partner is a web tool to predict interacting partners and binding models of a query protein sequence through structure complexes and a new scoring function. 3D-partner first utilizes IMPALA to identify homologous structures (templates) of a query from a heterodimer profile library. The interacting-partner sequence profiles of these templates are then used to search interacting candidates of the query from protein sequence databases (e.g. SwissProt) by PSI-BLAST. We developed a new scoring function, which includes the contact-residue interacting score (e.g. the steric, hydrogen bonds, and electrostatic interactions) and the template consensus score (e.g. couple-conserved residue and the template similarity scores), to evaluate how well the interfaces between the query and interacting candidates. Based on this scoring function, 3D-partner provides the statistic significance, the binding models (e.g. hydrogen bonds and conserved amino acids) and functional annotations of interacting partners. The correlation between experimental energies and predicted binding affinities of our scoring function is 0.91 on 275 mutated residues from the ASEdb. The average precision of the server is 0.72 on 563 queries and the execution time of this server for a query is ∼15 s on average. These results suggest that the 3D-partner server can be useful in protein-protein interaction predictions and binding model visualizations. The server is available online at: http://3D-partner.life.nctu.edu.tw

Anti-Neuroinflammatory Effects of the Calcium Channel Blocker Nicardipine on Microglial Cells: Implications for Neuroprotection

Background/Objective Nicardipine is a calcium channel blocker that has been widely used to control blood pressure in severe hypertension following events such as ischemic stroke, traumatic brain injury, and intracerebral hemorrhage. However, accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in neurodegeneration, and the effect of nicardipine on microglial activation remains unresolved. Methodology/Principal Findings In the present study, using murine BV-2 microglia, we demonstrated that nicardipine significantly inhibits microglia-related neuroinflammatory responses. Treatment with nicardipine inhibited microglial cell migration. Nicardipine also significantly inhibited LPS plus IFN-γ-induced release of nitric oxide (NO), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, nicardipine also inhibited microglial activation by peptidoglycan, the major component of the Gram-positive bacterium cell wall. Notably, nicardipine also showed significant anti-neuroinflammatory effects on microglial activation in mice in vivo. Conclusion/Significance The present study is the first to report a novel inhibitory role of nicardipine on neuroinflammation and provides a new candidate agent for the development of therapies for inflammation-related neurodegenerative diseases

Paternal genetic affinity between western Austronesians and Daic populations

<p>Abstract</p> <p>Background</p> <p>Austronesian is a linguistic family spread in most areas of the Southeast Asia, the Pacific Ocean, and the Indian Ocean. Based on their linguistic similarity, this linguistic family included Malayo-Polynesians and Taiwan aborigines. The linguistic similarity also led to the controversial hypothesis that Taiwan is the homeland of all the Malayo-Polynesians, a hypothesis that has been debated by ethnologists, linguists, archaeologists, and geneticists. It is well accepted that the Eastern Austronesians (Micronesians and Polynesians) derived from the Western Austronesians (Island Southeast Asians and Taiwanese), and that the Daic populations on the mainland are supposed to be the headstream of all the Austronesian populations.</p> <p>Results</p> <p>In this report, we studied 20 SNPs and 7 STRs in the non-recombining region of the 1,509 Y chromosomes from 30 China Daic populations, 23 Indonesian and Vietnam Malayo-Polynesian populations, and 11 Taiwan aboriginal populations. These three groups show many resemblances in paternal lineages. Admixture analyses demonstrated that the Daic populations are hardly influenced by Han Chinese genetically, and that they make up the largest proportion of Indonesians. Most of the population samples contain a high frequency of haplogroup O1a-M119, which is nearly absent in other ethnic families. The STR network of haplogroup O1a* illustrated that Indonesian lineages did not derive from Taiwan aborigines as linguistic studies suggest, but from Daic populations.</p> <p>Conclusion</p> <p>We show that, in contrast to the Taiwan homeland hypothesis, the Island Southeast Asians do not have a Taiwan origin based on their paternal lineages. Furthermore, we show that both Taiwan aborigines and Indonesians likely derived from the Daic populations based on their paternal lineages. These two populations seem to have evolved independently of each other. Our results indicate that a super-phylum, which includes Taiwan aborigines, Daic, and Malayo-Polynesians, is genetically educible.</p

Current trends in drug metabolism and pharmacokinetics.

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice