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Background: Diabetes and prediabetes are diagnosed differentially by Western and Chinese medicine. While Western medicine uses objective laboratory analysis of biochemical parameters to define the severity of diabetes and prediabetes, Chinese medicine uses a comprehensive approach that integrates observation, inquiry, pulse palpation, and tongue diagnosis. The medical information collected is then categorized into different syndromes. However, traditional methods of pulse and tongue diagnoses used to determine syndrome differentiation are highly subjective and skill dependent., Objective: This study aims to identify the gap in conventional traditional Chinese medicine (TCM) diagnostic techniques for syndrome differentiation analysis using contemporary diagnostic devices. We devised a protocol for a nonrandomized, exploratory, observational case-control study with equal allocations in 5 arms to investigate the syndrome differentiation of diabetes and prediabetes. We hypothesize that the TCM syndrome differentiation of diabetes and prediabetes in the tropical climate may differ from that defined based on the Chinese demographic. We also speculate that the high-frequency spectral energy may reflect a difference in pulse wave intensity and density between the healthy and diabetes groups., Methods: A total of 250 eligible participants will be equally assigned to 1 of 5 arms (healthy or subhealthy, prediabetes, diabetes, prediabetes with hypertension and dyslipidemia, and diabetes with hypertension and dyslipidemia). Participants aged 21-75 years, of any sex or race, and have been diagnosed with diabetes (fasting plasma glucose [FPG] of 7 mmol/L, or 2-hour plasma glucose [2hPG] of 11.1 mmol/L) or prediabetes (impaired FPG of 6.1-6.9 mmol/L, or impaired glucose tolerance with an 2hPG of 7.8-11 mmol/L) will be included. The Health Evaluation Questionnaire, Physical Activity Questionnaire, sugar intake assessment, Constitution in Chinese Medicine Questionnaire, radial pulse diagnosis, and tongue diagnosis will be performed in a single visit. ANOVA for continuous data and chi-square tests of independence will be used for categorical data assessments, with a level of P<.05 considered significant., Results: The recruitment is in progress. We anticipate that the study will conclude in June 2025. As of July 15, 2024, we have enrolled 140 individuals., Conclusions: To the best of our knowledge, this is the first study to use contemporary TCM diagnostic instruments to map expert and empirical knowledge of TCM to its scientific equivalents for the purpose of evaluating the syndrome differentiation of diabetes. We designed this protocol with the exploratory goal to examine objectively the syndrome differentiation of patients with diabetes and those with prediabetes using TCM diagnostic technologies. The data collected and evaluated under standardized conditions using these contemporary diagnostic devices will exhibit a higher degree of stability, hence yielding dependable and unbiased results for syndrome differentiation. Thus, our findings may potentially increase the accuracy of identification, diagnosis, treatment, and prevention of diabetes and prediabetes through a system of targeted treatment., Trial Registration: ClinicalTrials.gov NCT05563090; https://clinicaltrials.gov/ct2/show/NCT05563090., International Registered Report Identifier (irrid): DERR1-10.2196/56024., (©Hui Ping Ng, Shu Yun Chong, Yi Huan Li, Tong Hwee Goh, Ka Yii Pang, Michelle Jessica Pereira, Chin-Ming Huang. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.09.2024.)

Background: Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates., Objective: Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone., Methods: A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability., Results: Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals., Conclusions: The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models., Trial Registration: ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619., International Registered Report Identifier (irrid): DERR1-10.2196/54352., (©Bryan Yijia Tan, Chun Yue Tan, Tong Leng Tan, Su-Yin Yang, Gillian Long Szu Chew, Siang Ing Tan, Yu Chun Chua, Yew Wai Yan, Derrick Bing Quan Soh, Tong Hwee Goh, Pu Jue Ng, Yee Teck Ng, Swee Boey Kuan, Bo Siang Teo, Keng He Kong, Michelle Jessica Pereira, Hui Ping Ng. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 03.04.2024.)

Macrophages are the principal component of the innate immune system that are found in all tissues and play an essential role in development, homeostasis, tissue repair, and immunity. Clinical and experimental studies have shown that transcriptionally dynamic pro-inflammatory macrophages are involved in the pathogenesis of diet-induced obesity and insulin resistance. However, cell-intrinsic mechanisms must exist that bridle uncontrolled pro-inflammatory macrophage activation in metabolic organs and disease pathogenesis. In this study, we show that CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2) is an essential negative regulator of pro-inflammatory macrophage activation and inflammatory disease pathogenesis. Our in vivo studies show that myeloid-CITED2 deficiency significantly elevates high-fat diet (HFD)-induced expansion of adipose tissue volume, obesity, glucose intolerance, and insulin resistance. Moreover, myeloid-CITED2 deficiency also substantially augments HFD-induced adipose tissue inflammation and adverse remodeling of adipocytes. Our integrated transcriptomics and gene set enrichment analyses show that CITED2 deficiency curtails BCL6 signaling and broadly elevates BCL6-repressive gene target expression in macrophages. Using complementary gain- and loss-of-function studies, we found that CITED2 deficiency attenuates, and CITED2 overexpression elevates, inducible BCL6 expression in macrophages. At the molecular level, our analyses show that CITED2 promotes BCL6 expression by restraining STAT5 activation in macrophages. Interestingly, siRNA-mediated knockdown of STAT5 fully reversed elevated pro-inflammatory gene target expression in CITED2-deficient macrophages. Overall, our findings highlight that CITED2 restrains inflammation by promoting BCL6 expression in macrophages, and limits diet-induced obesity and insulin resistance.

The meridian and collateral theory in traditional Chinese medicine (TCM) provides practitioners with essential guidance about the complex network of meridians and collateral systems, as well as informing discussions on physiopathology, diagnoses, and treatments. Various translations have enabled nonnative Chinese to understand the intricacy of the meridian pathways. However, original meanings are easily lost in the text transcription and translation, leading to misinterpretation and confusion in the learning process. We set out to (a) review the standard glossary that describes the meridian pathways; (b) review English translations of the bladder meridian pathway in selected sources; and (c) propose more accurate English translations of both. Our proposed texts offer preliminary guidance on the standardization of the terminology describing the meridian pathways and remind us of the importance of being as precise as possible when translating TCM literature, so that the work retains its original meaning.

Macrophages are the principal innate immune cells that populate all major organs and provide the first line of cellular defense against infections and/or injuries. The immediate and early-responding macrophages must mount a robust pro-inflammatory response to protect the host by eliminating deleterious agents. The effective pro-inflammatory macrophage response requires the activation of complex transcriptional programs that modulate the dynamic regulation of inflammatory and metabolic gene expression. Therefore, transcription factors that govern pro-inflammatory and metabolic gene expression play an essential role in shaping the macrophage inflammatory response. Herein, we identify the basic helix-loop-helix family member e40 (BHLHE40), as a critical transcription factor that promotes broad pro-inflammatory and glycolytic gene expression by elevating HIF1α levels in macrophages. Our in vivo studies revealed that myeloid-BHLHE40 deficiency significantly attenuates macrophage and neutrophil recruitment to the site of inflammation. Our integrated transcriptomics and gene set enrichment analysis (GSEA) studies show that BHLHE40 deficiency broadly curtails inflammatory signaling pathways, hypoxia response, and glycolytic gene expression in macrophages. Utilizing complementary gain- and loss-of-function studies, our analyses uncovered that BHLHE40 promotes LPS-induced HIF1α mRNA and protein expression in macrophages. More importantly, forced overexpression of oxygen stable form of HIF1α completely reversed attenuated pro-inflammatory and glycolytic gene expression in BHLHE40-deficient macrophages. Collectively, these results demonstrate that BHLHE40 promotes macrophage pro-inflammatory gene expression and functions by elevating HIF1α expression in macrophages., (© 2021 Federation of American Societies for Experimental Biology.)

Objectives: To determine the difference in efficacy between distal and proximal acupoints in treating knee osteoarthritis., Design: Ninety-two eligible participants were randomly assigned into three groups: distal acupoint treatment group (DG), proximal acupoint treatment group (PG), and sham acupuncture control group (SG). Primary and secondary outcomes were compared before and after the intervention. Interventions . A single acupuncture treatment was applied at Quchi (LI11), Shaohai (HT3), and Tianjing (TE10) in DG participants; Yanglingquan (GB34), Yinlingquan (SP9), and Heding (EX-LE2) in PG participants; and Zhongwan (CV12) and Liangmen (ST21) in SG participants. Main outcome measures . The visual analog scale (VAS) and active and passive knee range of motion (ROM) were used primarily to evaluate the treatment efficacy. The radial pulse diagnosis was used as a secondary outcome measure to determine the changes in the spectral energy of the radial pulses., Results: The three groups had significant pain reduction after acupuncture ( p < 0.05). DG had the greatest difference in pre- and post-VAS scores. Compared with the control group, significant improvement was observed in DG active and passive ROM and in PG passive ROM ( p < 0.05). The high-frequency spectral energy of the left chi pulse in PG was significantly decreased, while the low-frequency spectral energy of the left cun pulse in PG and the left guan pulse in DG were significantly increased after acupuncture., Conclusions: Distal acupoints provide better pain relief and improve ROM than proximal acupoints in treating knee osteoarthritis. Significant changes in spectral energy were observed in the left cun , guan , and chi pulses, indicating pain relief and blood flow improvement after acupuncture., Competing Interests: The authors claim no conflicts of financial interest., (Copyright © 2021 Wan-Zhen Yu et al.)

Macrophages play crucial and diverse roles in the pathogenesis of inflammatory vascular diseases. Macrophages are the principal innate immune cells recruited to arterial walls to govern vascular homeostasis by modulating the proliferation of vascular smooth muscle cells, the reorganization of extracellular matrix components, the elimination of dead cells, and the restoration of normal blood flow. However, chronic sterile inflammation within the arterial walls draws inflammatory macrophages into intimal/neointimal regions that may contribute to disease pathogenesis. In this context, the accumulation and aberrant activation of macrophages in the neointimal regions govern the progression of inflammatory arterial wall diseases. Herein, we report that myeloid-hypoxia-inducible factor-1α (HIF1α) deficiency attenuates vascular smooth muscle cells and macrophage abundance in stenotic arteries and abrogates carotid neointima formation in vivo. The integrated transcriptomics, Gene Set Enrichment Analysis, metabolomics, and target gene evaluation showed that HIF1α represses oxidative phosphorylation, tricarboxylic acid cycle, fatty acid metabolism, and c-MYC signaling pathways while promoting inflammatory, glycolytic, hypoxia response gene expression in stenotic artery macrophages. At the molecular level, proinflammatory agents utilized STAT3 signaling pathways to elevate HIF1α expression in macrophages. Collectively, this study uncovers that macrophage-HIF1α deficiency restrains the pathogenesis of carotid artery stenosis by rewiring inflammatory and metabolic signaling pathways in macrophages., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Persistent neutrophilic inflammation is a hallmark of cystic fibrosis (CF). However, the mechanisms underlying this outstanding pathology remain incompletely understood. Here, we report that CFTR in myeloid immune cells plays a pivotal role in control of neutrophilic inflammation. Myeloid CFTR-Knockout (Mye-Cftr-/-) mice and congenic wild-type (WT) mice were challenged peritoneally with zymosan particles at different doses, creating aseptic peritonitis with varied severity. A high-dose challenge resulted in significantly higher mortality in Mye-Cftr-/- mice, indicating an intrinsic defect in host control of inflammation in mice whose myeloid cells lack CF. The low-dose challenge demonstrated an impaired resolution of inflammation in Mye-Cftr-/- mice, reflected by a significant overproduction of proinflammatory cytokines, including neutrophil chemokines MIP-2 and KC, and sustained accumulation of neutrophils. Tracing neutrophil mobilization in vivo demonstrated that myeloid CF mice recruited significantly more neutrophils than did WT mice. Pulmonary challenge with zymosan elicited exuberant inflammation in the lung and recapitulated the findings from peritoneal challenge. To determine the major type of cell that was primarily responsible for the over-recruitment of neutrophils, we purified and cultured ex vivo zymosan-elicited peritoneal neutrophils and macrophages. The CF neutrophils produced significantly more MIP-2 than did the WT counterparts, and peripheral blood neutrophils isolated from myeloid CF mice also produced significantly more MIP-2 after zymosan stimulation in vitro. These data altogether suggest that CFTR dysfunction in myeloid immune cells, especially neutrophils, leads to hyperinflammation and excessive neutrophil mobilization in the absence of infection. Thus, dysregulated inflammation secondary to abnormal or absent CFTR in myeloid cells may underlie the clinically observed neutrophilic inflammation in CF., (©2020 Society for Leukocyte Biology.)

Alcohol differentially affects human health, depending on the pattern of exposure. Moderate intake provides beneficial mood modulation and an anti-inflammatory effect, while excessive consumption leads to immunosuppression and various alcohol use disorders. The mechanism underlying this bi-phasic action mode of alcohol has not been clearly defined. Our previous publication demonstrated that ethanol, in the absence of glucocorticoids (GCs), induces expression of Glucocorticoid-Induced Leucine Zipper (GILZ), a key molecule that transduces GC anti-inflammatory effect through a non-canonical activation of glucocorticoid receptor (1). Here we report that similar short-chain alcohols, such as ethanol, propanol and isopropanol, share the same property of upregulating GILZ gene expression, and blunt cell inflammatory response in vitro . When mice were exposed to these alcohols, GILZ gene expression in immune cells was augmented in a dose-dependent manner. Monocytes and neutrophils were most affected. The short-chain alcohols suppressed host inflammatory response to lipopolysaccharide (LPS) and significantly reduced LPS-induced mortality. Intriguingly, propanol and isopropanol displayed more potent protection than ethanol at the same dose. Inhibition of ethanol metabolism enhanced the ethanol protective effect, suggesting that it is ethanol, not its derivatives or metabolites, that induces immune suppression. Taken together, short-chain alcohols per se upregulate GILZ gene expression and provide immune protection against LPS toxicity, suggesting a potential measure to counter LPS septic shock in a resource limited situation., (Copyright © 2020 Ng, Jennings, Nelson and Wang.)

Macrophages are the professional phagocytes that protect the host from infection or injury. Tissue microenvironment at the site of injury and inflammation is characterized by low oxygen concentration and poor supply of nutrients. The responding macrophages have to advance against oxygen and nutrient gradients to reach the site of inflammation to perform host protection, and tissue repair functions. Thus, evolution has fashioned macrophages to orchestrate a coordinated inflammatory and hypoxic gene program to mount an effective immune response. Here, we discovered that Kruppel-like factor 6 (KLF6) governs macrophage functions by promoting inflammatory and hypoxic response gene programming. Our in vivo studies revealed that myeloid-KLF6-deficient mice were highly resistant to endotoxin-induced systemic inflammatory response syndrome symptomatology and mortality. Using complementary gain- and loss-of-function studies, we observed that KLF6 overexpression elevate and KLF6 deficiency attenuate inducible HIF1α expression in macrophages. Our integrated transcriptomics and gene set enrichment analysis studies uncovered that KLF6 deficiency attenuates broad inflammatory and glycolytic gene expression in macrophages. More importantly, overexpression of oxygen stable HIF1α reversed attenuated proinflammatory and glycolytic gene expression in KLF6-deficient macrophages. Collectively, our studies uncovered that KLF6 govern inflammatory and hypoxic response by regulating HIF1α expression in macrophage., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology.)

Acupuncture is a core discipline in traditional Chinese medicine (TCM) and has been practised in China for centuries. In traditional acupuncture, pulse palpation is an important clinical diagnostic technique that guides practitioners in their treatment strategies as they evaluate the effectiveness of the treatment. This paper provides the findings of our investigation of acupuncture's effect on specific radial pulse spectral energies in 41 individuals with lower back pain (LBP), in response to a single acupuncture treatment delivered bilaterally at acupoints BL23, BL25, and BL40. Baseline assessments (vital signs and radial pulse diagnoses), primary outcome measures (radial pulse diagnoses), and secondary outcome measures (the Faces Pain Scale-Revised (FPS-R) and fingertip-to-floor (FTF) tests) were performed at specified intervals before and after the intervention. Our study provides novel information about the effects of acupuncture on the radial pulse spectral energy in individuals with different types of LBP. Our findings suggest that the right Chi pulse is an effective indicator to assess the effects of acupuncture in individuals with fixed, distended, or sharp pain, whereas the left Guan pulse is a potentially useful diagnostic technique to determine acupuncture's effects in individuals with dull, aching pain. The acupoints BL23, BL25, and BL40 provide effective treatment for LBP. Study participants with dull, aching pain had a significant improvement in their lumbar ranges of motion, and their pain rating scores were markedly decreased after acupuncture treatment., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2019 Hui-Ping Ng et al.)

Macrophage-mediated inflammation is an explicitly robust biologic response that plays a critical role in maintaining tissue homeostasis by eliminating deleterious agents. These tissue macrophages tailor appropriate responses to external cues by altering inflammatory gene expression. Therefore, transcription factors and regulators that modulate inflammatory gene expression play an essential role in shaping the macrophage inflammatory response. Here, we identify that Kruppel-like factor (KLF)6 promotes inflammation by restraining microRNA-223 (miR-223) expression in macrophages. We uncovered that pro- and anti-inflammatory agents oppositely regulate KLF6 and miR-223 expression in macrophages. Using complementary gain- and loss-of-function studies, we observed that overexpression of KLF6 attenuates and deficiency of KLF6 elevates miR-223 expression in macrophages. Furthermore, heightened miR-223 expression in KLF6-deficient macrophages significantly attenuates inducible proinflammatory gene expression. Concordantly, myeloid- Klf6 deficiency significantly curbs diet-induced adipose tissue inflammation, obesity, glucose intolerance, and insulin resistance. At the molecular level, KLF6 directly represses miR-223 expression by occupying its promoter region. More importantly, genetic inhibition of miR-223-3P in KLF6-deficient macrophages completely reversed attenuated proinflammatory gene expression in macrophages. Collectively, our studies reveal that KLF6 promotes proinflammatory gene expression and functions by repressing miR-223 expression in macrophages.-Kim, G.-D., Ng, H. P., Patel, N., Mahabeleshwar, G. H. Kruppel-like factor 6 and miR-223 signaling axis regulates macrophage-mediated inflammation.

In recent years, transition metal complexes with their prominent photophysical properties have emerged as versatile chemosensors to probe different target analytes, including metal ions. By incorporating specific metal ion receptors, various iridium(III) complex-based cation sensors have been developed using different mechanisms. In this review, we survey examples of iridium(III) complex-based metal ion chemosensors that have been reported in the literature. Their design, mechanism and outlook will also be discussed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The characteristics of radial pressure pulse waves (RPPW) provide an essential diagnostic technique in Traditional Chinese Medicine (TCM). The purpose of this research is to develop a study protocol that integrates the concept of TCM and traditional acupuncture treatment with modern scientific tools utilizing a quasi-experimental design. We will investigate the effects of acupuncture on the RPPW in study participants with low back pain (LBP) using modern tools, including the pulse sphygmograph, the fingertip-to-floor test, the Faces Pain Scale-Revised, the Oswestry Disability Index, the Health Status Questionnaire, and the Constitution in Chinese Medicine Questionnaire., Methods: We will attempt to recruit 80 eligible subjects with LBP based on our predefined inclusion and exclusion criteria. Acupuncture intervention will be performed bilaterally on Shenshu (BL23), Dachangshu (BL25) and Weizhong (BL40) for 20 min. Objective and subjective baseline assessments and outcome evaluations will be performed at a specific time before and after the intervention. This paper describes the methods of our original research approved by the China Medical University Hospital's Research Ethics Committee. Recruitment is in progress and data collection will continue until March 2019., Conclusions: To our knowledge, this preliminary study is the first attempt to investigate the effects of acupuncture on the RPPW in LBP subjects using a pulse sphygmograph and other modern tools. The findings will also investigate the effectiveness of the selected acupuncture point combinations for LBP. We hope this preliminary study will provide a basic foundation for a large-scale research study that involves randomisation in the future.

Background: Bell's palsy is the most frequent cause of unilateral peripheral facial palsy, a common condition that third of patients can have inadequate recovery and subsequent physical and social impairments. The largely ineffective and even controversial nature of the various medical and surgical treatment options means that novel, alternative approaches are needed. In preclinical and clinical evidence, low-level laser therapy (LLLT) has demonstrated the ability to regenerate peripheral nerves. Laser acupuncture treatment (LAT), the stimulation of traditional acupoints with low-intensity, non-thermal laser irradiation, is a common treatment modality, but its efficacy in chronic Bell's palsy is undetermined. This study aims to evaluate the efficacy of LAT in patients experiencing inadequate recovery from Bell's palsy., Methods: This 2-armed, parallel, randomized, subject-assessor-blinded, single-center, sham-controlled pilot trial will randomly assign 32 eligible patients into either a real LAT group (n = 16) or a sham LAT group (n = 16). The real LAT group will receive 3 LAT sessions each week for 6 weeks (a total of 18 sessions), delivered to acupoints corresponding with the affected side of the face. The sham LAT group will receive the same treatment as the real LAT group, but with a sham laser device. The primary outcome measure will be the change from baseline at week 6 in the Facial Disability Index score. Secondary outcomes will monitor changes during treatment in the House-Brackmann and Sunnybrook facial nerve grading systems and stiffness scale, at weeks 1, 3, and 6., Discussion: To the best of our knowledge, this double-blind, randomized, sham-controlled trial is the first such investigation into the efficacy of LAT in chronic Bell's palsy. Clinical trials using LLLT have shown positive therapeutic effects in acute Bell's palsy, although as yet, the feasibility and efficacy of LAT remain unclear in patients experiencing inadequate recovery from Bell's palsy., Trial Registration: This trial protocol has been approved by the Research Ethics Committee of the China Medical University Hospital, Taichung, Taiwan (Protocol ID: CMUH107-REC1-030) also registered at ClinicalTrials.gov (identifier no. NCT03592797).

Cystic fibrosis (CF), one of the most common genetic disorders, is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In spite of significant improvement in patient life expectancy, the disease remains lethal and incurable. Clinically, CF lung disease claims the most morbidity and mortality, characterized by chronic bacterial infection, persistent neutrophilic inflammation, and purulent small airway obstruction. Although all these manifestations are highly associated with neutrophils, the actual role of this phagocyte in the disease pathogenesis has not been fully appreciated. One of the major obstacles impeding such progress is the lack of CF neutrophil cell lines. Taking advantage of the new CRISPR/Cas9 gene-editing technology, we have generated a homozygous ΔF508-CF promyelocytic cell line from HL-60 cells, from which unlimited CF neutrophil cells can be differentiated. The derived cells showed defective CFTR presentation, deficient phagosomal hypochlorous acid (HOCl) production, and compromised microbial killing. Such a phenotype recapitulates that of primary neutrophils from CF patients. Thus, the established human CF promyelocytic cell line should be a useful tool for future CF basic research and drug screening., (Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Transition metal complexes have attracted interest in the fields of cancer therapy, medical and environmental detection, and materials of organic light-emitting diodes (OLED). Recently, iridium(iii) complexes have been explored in a reaction based way for luminescence monitoring and imaging due to their salient photophysical properties, including large Stokes shifts, long-lived luminescence and high luminescent quantum yields. This frontier article will introduce recent developments and applications of iridium(iii) complexes as luminescent probes for ions and biomolecules. Our outlook for this class of complexes is also discussed.

As technology advances, more modern medical devices are developed to help the physicians in performing objective assessment and diagnosis. In this study, our main objective was to evaluate the clinical application of the low voltage Meridian Energy Detection System in assessing the electrodermal activity (EDA) of the specific acupoints in a specific age group of healthy individuals and to assess the difference in the energy overview between the genders and specific time of assessment. 43 young healthy adults were recruited in a single group, nonrandomized, evaluation study. Written informed consent of each participant was obtained prior to the assessments. Results on energy overview between genders and specific time of assessment as well as factors influencing EDA were discussed. It was concluded that the study using Meridian Energy Detection System in healthy individuals provided an understanding of the difference in energy level of the meridians between the genders. Male healthy individuals had significantly higher values for Physical Status as well as Yin and Yang energy while female healthy individuals had significantly higher values for Mental Health and Autonomic Nervous System. There was no significant difference when comparing the assessments at the specific time of assessment. Hence there was no specific time in using the device. However, due to the limitation of the sample size and the healthy subjects, future research can be designed to investigate whether the time of assessment can affect the results in individuals with specific disease conditions in larger scale. It may merit further studies on the application of such device as preliminary diagnosis of the overall conditions and investigate the treatment efficacy by observing the change in the meridian energy level.

Acute alcohol exposure suppresses cell inflammatory response. The underlying mechanism has not been fully defined. Here we report that alcohol was able to activate glucocorticoid receptor (GR) signaling in the absence of glucocorticoids (GCs) and upregulated glucocorticoid-induced leucine zipper ( gilz ), a prominent GC-responsive gene. Such a non-canonical activation of GR was not blocked by mifepristone, a potent GC competitor. The proximal promoter of gilz , encompassing five GC-responsive elements (GREs), was incorporated and tested in a luciferase reporter system. Deletion and/or mutation of the GREs abrogated the promoter responsiveness to alcohol. Thus, the GR-GRE interaction transduced the alcohol action on gilz . Alcohol induced GR nuclear translocation, which was enhanced by the alcohol dehydrogenase inhibitor fomepizole, suggesting that it was alcohol, not its metabolites, that engendered the effect. Gel mobility shift assay showed that unliganded GR was able to bind GREs and such interaction withstood clinically relevant levels of alcohol. GR knockout via CRISPR/Cas9 gene targeting or GILZ depletion via small RNA interference diminished alcohol suppression of cell inflammatory response to LPS. Thus, a previously unrecognized, non-canonical GR activation of gilz is involved in alcohol modulation of cell immune response.

Background There is a lack of large comprehensive studies in developing countries on paediatric in-patient prescribing errors in different settings. Objectives To determine the characteristics of in-patient prescribing errors among paediatric patients. Setting General paediatric wards, neonatal intensive care units and paediatric intensive care units in government hospitals in Malaysia. Methods This is a cross-sectional multicentre study involving 17 participating hospitals. Drug charts were reviewed in each ward to identify the prescribing errors. All prescribing errors identified were further assessed for their potential clinical consequences, likely causes and contributing factors. Main outcome measures Incidence, types, potential clinical consequences, causes and contributing factors of the prescribing errors. Results The overall prescribing error rate was 9.2% out of 17,889 prescribed medications. There was no significant difference in the prescribing error rates between different types of hospitals or wards. The use of electronic prescribing had a higher prescribing error rate than manual prescribing (16.9 vs 8.2%, p < 0.05). Twenty eight (1.7%) prescribing errors were deemed to have serious potential clinical consequences and 2 (0.1%) were judged to be potentially fatal. Most of the errors were attributed to human factors, i.e. performance or knowledge deficit. The most common contributing factors were due to lack of supervision or of knowledge. Conclusions Although electronic prescribing may potentially improve safety, it may conversely cause prescribing errors due to suboptimal interfaces and cumbersome work processes. Junior doctors need specific training in paediatric prescribing and close supervision to reduce prescribing errors in paediatric in-patients.

Surface modification is an important step in production of medical implants. Surface roughening creates additional surface area to enhance the bonding between the implant and the bone. Recent research provided a means to alter the microstructure of titanium by severe plastic deformation (SPD) in order to increase its strength, and thereby reduce the size of the implants (specifically, their diameter). The purpose of the present study was to examine the effect of bulk microstructure of commercially pure titanium with coarse-grained (CG) and ultrafine-grained (UFG) bulk structure on the surface state of these materials after surface modification by sand blasting and acid etching (SLA). It was shown that SLA-modified surface characteristics, in particular, roughness, chemistry, and wettability, were affected by prior SPD processing. Additionally, biocompatibility of UFG titanium was examined using osteosarcoma cell line SaOS-2 and primary human adipose-derived mesenchymal stem cell (adMSC) cultures. Enhanced cell viability as well as increased matrix mineralization during osteogenic differentiation of MSCs on the surface of ultrafine-grained titanium was shown., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel, plays critical roles in phagocytic host defense. However, how activated neutrophils regulate CFTR channel distribution subcellularly is not well defined. To investigate, we tested multiple Abs against different CFTR domains, to examine CFTR expression in human peripheral blood neutrophils by flow cytometry. The data confirmed that resting neutrophils had pronounced CFTR expression. Activation of neutrophils with soluble or particulate agonists did not significantly increase CFTR expression level, but induced CFTR redistribution to cell surface. Such CFTR mobilization correlated with cell-surface recruitment of formyl-peptide receptor during secretory vesicle exocytosis. Intriguingly, neutrophils from patients with ΔF508-CF, despite expression of the mutant CFTR, showed little cell-surface mobilization upon stimulation. Although normal neutrophils effectively targeted CFTR to their phagosomes, ΔF508-CF neutrophils had impairment in that process, resulting in deficient hypochlorous acid production. Taken together, activated neutrophils regulate CFTR distribution by targeting this chloride channel to the subcellular sites of activation, and ΔF508-CF neutrophils fail to achieve such targeting, thus undermining their host defense function., (© Society for Leukocyte Biology.)

Surface modification techniques are widely used to enhance the biological response to the implant materials. These techniques generally create a roughened surface, effectively increasing the surface area thus promoting cell adhesion. However, a negative side effect is a higher susceptibility of a roughened surface to failure due to the presence of multiple stress concentrators. The purpose of the study reported here was to examine the effects of surface modification by sand blasting and acid-etching (SLA) on the microstructure and fatigue performance of coarse-grained and ultrafine-grained (UFG) commercially pure titanium. Finer grain sizes, produced by equal channel angular pressing, resulted in lower values of surface roughness in SLA-processed material. This effect was associated with greater resistance of the UFG structure to plastic deformation. The fatigue properties of UFG Ti were found to be superior to those of coarse-grained Ti and conventional Ti-6Al-4V, both before and after SLA-treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Fcγ receptors (FcγRs) are classified as activating (FcγRI, III, and IV) and inhibitory (FcγRII) receptors. We have reported that deletion of activating FcγRs in apolipoprotein E (apoE) single knockout mice attenuated atherosclerosis. In this report, we investigated the hypothesis that deficiency of inhibitory FcγRIIb exacerbates atherosclerosis., Approach and Results: ApoE-FcγRIIb double knockout mice, congenic to the C57BL/6 (apoE-FcγRIIbB6 (-/-)), were generated and atherosclerotic lesions were assessed. In contrary to our hypothesis, when compared with apoE single knockout mice, arterial lesions were significantly decreased in apoE-FcγRIIbB6 (-/-) male and female mice fed chow or high-fat diets. Chimeric mice generated by transplanting apoE-FcγRIIbB6 (-/-) marrow into apoE single knockout mice also developed reduced lesions. CD4(+) T cells from apoE-FcγRIIbB6 (-/-) mice produced higher levels of interleukin-10 and transforming growth factor-β than their apoE single knockout counterparts. As our findings conflict with a previous report using apoE-FcγRIIb129/B6 (-/-) mice on a mixed genetic background, we investigated whether strain differences contributed to the anti-inflammatory response. Macrophages from FcγRIIb129/B6 (-/-) mice on a mixed genetic background produced more interleukin-1β and MCP-1 (monocyte chemoattractant protein-1) in response to immune complexes, whereas congenic FcγRIIbB6 (-/-) mice generated more interleukin-10 and significantly less interleukin-1β. Interestingly, the expression of lupus-associated slam genes, located in proximity to fcgr2b in mouse chromosome 1, is upregulated only in mixed FcγRIIb129/B6 (-/-) mice., Conclusions: Our findings demonstrate a detrimental role for FcγRIIb signaling in atherosclerosis and the contribution of anti-inflammatory cytokine responses in the attenuated lesions observed in apoE-FcγRIIbB6 (-/-) mice. As 129/sv genome-derived lupus-associated genes have been implicated in lupus phenotype in FcγRIIb129/B6 (-/-) mice, our findings suggest possible epistatic mechanism contributing to the decreased lesions., (© 2015 American Heart Association, Inc.)

Cystic fibrosis (CF) is a common and deadly inherited disease, caused by mutations in the CFTR gene that encodes a cAMP-activated chloride channel. One outstanding manifestation of the disease is the persistent bacterial infection and inflammation in the lung, which claims over 90% of CF mortality. It has been debated whether neutrophil-mediated phagocytic innate immunity has any intrinsic defect that contributes to the host lung defense failure. Here we compared phagosomal CFTR targeting, hypochlorous acid (HOCl) production, and microbial killing of the neutrophils from myeloid Cftr-inactivated (Myeloid-Cftr-/-) mice and the non-inactivated control (Cftrfl10) mice. We found that the mutant CFTR that lacked Exon-10 failed to target to the neutrophil phagosomes. This dysfunction resulted in impaired intraphagosomal HOCl production and neutrophil microbial killing. In vivo lung infection with a lethal dose of Pseudomonas aeruginosa caused significantly higher mortality in the myeloid CF mice than in the controls. The myeloid-Cftr-/- lungs were deficient in bacterial clearance, and had sustained neutrophilic inflammation and stalled transition from early to late immunity. These manifestations recapitulated the symptoms of human CF lungs. The data altogether suggest that myeloid CFTR expression is critical to normal host lung defense. CFTR dysfunction in neutrophils compromises the phagocytic innate immunity, which may predispose CF lungs to infection.

Recent studies showed loss of CD36 or scavenger receptor-AI/II (SR-A) does not ameliorate atherosclerosis in a hyperlipidemic mouse model, suggesting receptors other than CD36 and SR-A may also contribute to atherosclerosis. In this report, we show that apolipoprotein E (apoE)-CD16 double knockout (DKO; apoE-CD16 DKO) mice have reduced atherosclerotic lesions compared with apoE knockout mice. In vivo and in vitro foam cell analyses showed apoE-CD16 DKO macrophages accumulated less neutral lipids. Reduced foam cell formation in apoE-CD16 DKO mice is not due to change in expression of CD36, SR-A, and LOX-1. This led to a hypothesis that CD16 may have scavenger receptor activity. We presented evidence that a soluble form of recombinant mouse CD16 (sCD16) bound to malondialdehyde-modified low-density lipoprotein (MDALDL), and this binding is blocked by molar excess of MDA- modified BSA and anti-MDA mAbs, suggesting CD16 specifically recognizes MDA epitopes. Interestingly, sCD16 inhibited MDALDL binding to macrophage cell line, as well as soluble forms of recombinant mouse CD36, SR-A, and LOX-1, indicating CD16 can cross-block MDALDL binding to other scavenger receptors. Anti-CD16 mAb inhibited immune complex binding to sCD16, whereas it partially inhibited MDALDL binding to sCD16, suggesting MDALDL binding site may be in close proximity to the immune complex binding site in CD16. Loss of CD16 expression resulted in reduced levels of MDALDL-induced proinflammatory cytokine expression. Finally, CD16-deficient macrophages showed reduced MDALDL-induced Syk phosphorylation. Collectively, our findings suggest scavenger receptor activity of CD16 may, in part, contribute to the progression of atherosclerosis., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Purpose: Inflammation is a hallmark of many diseases, such as atherosclerosis, autoimmune diseases, obesity, and cancer. Isoflavone-free soy protein diet (SPI(-)) has been shown to reduce atherosclerotic lesions in a hyperlipidemic mouse model compared to casein (CAS)-fed mice, despite unchanged serum lipid levels. However, possible mechanisms contributing to the athero-protective effect of soy protein remain unknown. Therefore, we investigated whether and how SPI(-) diet inhibits inflammatory responses associated with atherosclerosis., Methods: Apolipoprotein E knockout (apoE-/-) mice (5-week) were fed CAS or SPI(-) diet for 1 or 5 week to determine LPS- and hyperlipidemia-induced acute and chronic inflammatory responses, respectively. Expression of NF-κB-dependent inflammation mediators such as VCAM-1, TNF-α, and MCP-1 were determined in aorta and liver. NF-κB, MAP kinase, and AKT activation was determined to address mechanisms contributing to the anti-inflammatory properties of soy protein/peptides., Results: Isoflavone-free soy protein diet significantly reduced LPS-induced VCAM-1 mRNA and protein expression in aorta compared to CAS-fed mice. Reduced VCAM-1 expression in SPI(-)-fed mice also paralleled attenuated monocyte adhesion to vascular endothelium, a critical and primary processes during inflammation. Notably, VCAM-1 mRNA and protein expression in lesion-prone aortic arch was significantly reduced in apoE-/- mice fed SPI(-) for 5 weeks compared with CAS-fed mice. Moreover, dietary SPI(-) potently inhibited LPS-induced NF-κB activation and the subsequent upregulation of pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β, and MCP-1. Interestingly, SPI(-) inhibited NF-κB-dependent inflammatory responses by targeting I-κB phosphorylation and AKT activation with no effect on MAP kinase pathway. Of the five putative soy peptides, four of the soy peptides inhibited LPS-induced VCAM-1, IL-6, IL-8, and MCP-1 protein expression in human vascular endothelial cells in vitro., Conclusions: Collectively, our findings suggest that anti-inflammatory properties of component(s) of soy protein/peptides may be a possible mechanism for the prevention of chronic inflammatory diseases such as atherosclerosis.

Breast cancer incidence is increasing worldwide. Early detection is critical for long-term patient survival, as is monitoring responses to chemotherapy for management of the disease. Magnetic resonance imaging and spectroscopy (MRI/MRS) has gained in importance in the last decade for the diagnosis and monitoring of breast cancer therapy. The sensitivity of MRI/MRS for anatomical delineation is very high and the consensus is that MRI is more sensitive in detection than x-ray mammography. Advantages of MRS include delivery of biochemical information about tumor metabolism, which can potentially assist in the staging of cancers and monitoring responses to treatment. The roles of MRS and MRI in screening and monitoring responses to treatment of breast cancer are reviewed here. We rationalize how it is that different histological types of breast cancer are differentially detected and characterized by MR methods.

Aim: This study aims to reduce the incidence of falls in paediatric inpatients aged 3 and below by implementing fall prevention strategies., Methods: The Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice programmes were used for this project. The project was carried out in three phases over a 4-month period from March to June 2011. A fall prevention poster was introduced during the implementation phase, and pre- and post-implementation audits were carried out in a 43-bed acute care paediatric ward in Singapore, with a sample size of 30., Results: The audit result of Criterion 1, evaluating the effectiveness of the fall prevention measures, improved by 13%, to 93%. Criterion 2, measuring nurses' compliance in the regular reinforcement of safety, improved significantly by 27%, to 40%. However, Criterion 3, which measured nurses' compliance in identifying patients at high risk of falls by placing a green identification wrist tag on such patients, decreased by 23%, to 50%., Discussion: A multi-language poster on fall prevention was strategically positioned at the foot of all the cots. The poster served as an effective reminder and communication method between nurses and caregivers and also among caregivers of the child. Caregivers' increased awareness and knowledge of fall prevention contributed to a 50% decrease in fall incidence of patients aged 3 and below in the presence of a caregiver from January to June 2011, as compared with the incidence rate in 2010., Conclusion: This project has shown that fall incidents can be reduced when caregivers' awareness of fall prevention measures in the hospital setting were to be improved. The poster on fall prevention has increased caregivers' awareness and reduced inpatient falls in the acute care setting. The pre- and post-implementation audits showed that the presence of a poster on fall prevention to remind parents/caregivers to raise and securely lock the cot rails at all times was effective in reducing the number of falls for children aged 3 years and below. The experience gained from this project was that communication to every staff member and caregivers is essential in implementing practice change. As a result of the study, the hospital plans to implement constant monitoring and reminders to nurses and caregivers to improve compliance to the recommended measures on fall prevention in the near future., (© 2013 The Authors. International Journal of Evidence-Based Healthcare © 2013 The Joanna Briggs Institute.)

The recent emergence of the focused ion-beam (FIB) microscope as a dedicated specimen preparation tool for transmission electron microscopy (TEM) has extended the reach of TEM to a wider variety of problems in materials science. This paper highlights three examples of using FIB-SEM lift-out techniques for preparing site-specific and crystallographic orientation-specific thin-foil specimens. An in situ lift-out technique used to extract thin foils from across a local grain boundary in bulk Al alloy and from individual fine Al atomised powder particles (down to 20μm in diameter) was performed with real-time secondary electron imaging within the chamber of a FIB-SEM system. In conjunction with electron backscatter diffraction (EBSD), the FIB is used for extracting TEM foil with a specific crystallographic orientation aligned normal to the broad plane of the foil. The above technique has been demonstrated using a dual-phase Ti-Si alloy for the exploration of orientation relationship between constituent phases. Furthermore, it is suggested that FIB is more applicable for preparing thin foils from hydrogen-sensitive metals (such as titanium alloys) than conventional thinning techniques, which tend to induce ambiguous artifacts in these foils., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The effect of grain refinement of commercial purity titanium by equal channel angular pressing (ECAP) on its mechanical performance and bone tissue regeneration is reported. In vivo studies conducted on New Zealand white rabbits did not show an enhancement of biocompatibility of ECAP-modified titanium found earlier by in vitro testing. However, the observed combination of outstanding mechanical properties achieved by ECAP without a loss of biocompatibility suggests that this is a very promising processing route to bioimplant manufacturing. The study thus supports the expectation that commercial purity titanium modified by ECAP can be seen as an excellent candidate material for bone implants suitable for replacing conventional titanium alloy implants.

Though the presence of antioxidized low-density lipoprotein IgG is well documented in clinical and animal studies, the role for FcγRs to the progression of atherosclerosis has not been studied in detail. In the current study, we investigated the role for activating FcγR in the progression of atherosclerosis using apolipoprotein E (apoE)-Fcγ-chain double-knockout (DKO) mice. Relative to apoE knockout (KO) mice, arterial lesion formation was significantly decreased in apoE-Fcγ-chain DKO mice. Bone marrow chimera studies showed reduced lesions in apoE KO mice receiving the bone marrow of apoE-Fcγ-chain DKO mice. Compared to apoE KO mice, antioxidized low-density lipoprotein IgG1 (Th2) and IgG2a (Th1), IL-10, and IFN-γ secretion by activated T cells was increased in apoE-Fcγ-chain DKO mice. These findings suggest that reduced atherosclerotic lesion in apoE-Fcγ-chain DKO mice is not due to a Th1/Th2 imbalance. Interestingly, the number of Th17 cells and the secretion of IL-17 by activated CD4(+) cells were decreased in apoE-Fcγ-chain DKO mice. Notably, the number of regulatory T cells, expression of mRNA, and secretion of TGF-β and IL-10 were increased in apoE-Fcγ-chain DKO mice. Furthermore, secretions of IL-6 and STAT-3 phosphorylation essential for Th17 cell genesis were reduced in apoE-Fcγ-chain DKO mice. Importantly, decrease in Th17 cells in apoE-Fcγ-chain DKO mice was due to reduced IL-6 release by APC of apoE-Fcγ-chain DKO mice. Collectively, our data suggest that activating FcγR promotes atherosclerosis by inducing a Th17 response in the hyperlipidemic apoE KO mouse model.

The intercellular adhesive molecule, ICAM-L, of Leishmania amazonensis is known to block the attachment as well as internalisation of Leishmania for infection in host macrophages. We employed monoclonal antibodies (mAb) to the surface molecules of a macrophage to block the attachment of ICAM-L to the macrophage surface and identified that CD68 macrosialin is likely the receptor molecule on the macrophage for ICAM-L. We then demonstrated physical interaction between ICAM-L and macrosialin by co-immunoprecipitation of macrosialin with ICAM-L or vice versa. Finally, macrosialin is expressed in macrosialin-negative murine fibroblast cell line NCTC clone 2555 and demonstrates that both ICAM-L and promastigotes of L. amazonensis can bind to the CD68 transfectant. We thus conclude that CD68 macrosialin is the receptor on host macrophages for ICAM-L. Also, involvement of ICAM-L-macrosialin interaction in other Leishmania species and other mammalian macrophages were demonstrated, indicating the biological relevance of this ligand-receptor interaction.

A method is proposed for 3D segmentation and quantification of the masseter muscle from magnetic resonance (MR) images, which is often performed in pre-surgical planning and diagnosis. Because of a lack of suitable automatic techniques, a common practice is for clinicians to manually trace out all relevant regions from the image slices which is extremely time-consuming. The proposed method allows significant time savings. In the proposed method, a patient-specific masseter model is built from a test dataset after determining the dominant slices that represent the salient features of the 3D muscle shape from training datasets. Segmentation is carried out only on these slices in the test dataset, with shape-based interpolation then applied to build the patient-specific model, which serves as a coarse segmentation of the masseter. This is first refined by matching the intensity distribution within the masseter volume against the distribution estimated from the segmentations in the dominant slices, and further refined through boundary analysis where the homogeneity of the intensities of the boundary pixels is analyzed and outliers removed. It was observed that the left and right masseter muscles' volumes in young adults (28.54 and 27.72 cm(3)) are higher than those of older (ethnic group removed) adults (23.16 and 22.13 cm(3)). Evaluation indicates good agreement between the segmentations and manual tracings, with average overlap indexes for the left and right masseters at 86.6% and 87.5% respectively.

Objectives: The objective of this study was to quantitatively evaluate the correlation between left and right masticatory muscle volumes in normal subjects., Methods: Contiguous 1 mm MR scans were obtained of 12 normal adult subjects aged 20-25 years using a Siemens 1.5 T MR scanner. The volumes of the human masticatory muscles (masseter, lateral and medial pterygoid) were measured from the scans using our previously proposed method. To test for inter- and intraobserver reproducibility, measurements were performed by two users on two separate occasions, with a span of 2 weeks between them and with the previous results blinded. Good inter- and intraobserver reproducibility was achieved in our study., Results: The mean volumes for left and right masseters, and lateral and medial pterygoids were 29.54 cm3, 29.65 cm3, 9.47 cm3, 10.23 cm3, 8.69 cm3 and 8.92 cm3, respectively. The Pearson correlation coefficients between the volumes of the left and right masseters, lateral and medial pterygoids are 0.969, 0.906 and 0.924, respectively., Conclusions: The computed volumes of the masticatory muscles show a strong correlation between the volumes of the left and right masseters, and lateral and medial pterygoids for normal adult subjects. The total masticatory muscle volume on the left and right sides of normal subjects is similar.

Objective: To determine the fertility and abortion rates in a mouse model of autoimmune thyroiditis and its relationship with circulating anti-thyroid peroxidase (TPO) antibody., Design: Experimental animal study., Setting: University research laboratory., Animal(s): C57bl/6 mice., Intervention(s): Female C57bl/6 mice immunized with recombinant mouse TPO (rmTPO) in complete Freund adjuvant (CFA) or glutathione-S-transferase (GST-CFA) were allowed to mate. The pregnant mice were killed on day 14 of pregnancy for assessment of fetal development. The effects of TPO antibody on preimplantation embryo development and implantation rate were also studied., Main Outcome Measure(s): Litter size, resorption rate, preimplantation embryo development, and implantation rate., Result(s): All of the mice immunized with rmTPO-CFA possessed anti-TPO antibody. They had reduced litter size and increased incidence of resorbed fetus compared with the control. Higher serum TSH levels, but not T(4) levels, were demonstrated after rmTPO-CFA immunization. Anti-TPO antibody bound to preimplantation embryos. Treatment of the embryos with the antibody marginally decreased the formation of 3/4-cell embryos but had no effect on the subsequent development and implantation compared with the nonimmune control sera., Conclusion(s): Autoimmune thyroiditis is associated with reduced fertility and higher incidence of fetal loss. The anti-TPO antibody may affect post-implantation embryo development, leading to fetal loss.

The watershed algorithm always produces a complete division of the image. However, it is susceptible to over-segmentation and sensitivity to false edges. In medical images this leads to unfavorable representations of the anatomy. We address these drawbacks by introducing automated thresholding and post-segmentation merging. The automated thresholding step is based on the histogram of the gradient magnitude map while post-segmentation merging is based on a criterion which measures the similarity in intensity values between two neighboring partitions. Our improved watershed algorithm is able to merge more than 90% of the initial partitions, which indicates that a large amount of over-segmentation has been reduced. To further improve the segmentation results, we make use of K-means clustering to provide an initial coarse segmentation of the highly textured image before the improved watershed algorithm is applied to it. When applied to the segmentation of the masseter from 60 magnetic resonance images of 10 subjects, the proposed algorithm achieved an overlap index (kappa) of 90.6%, and was able to merge 98% of the initial partitions on average. The segmentation results are comparable to those obtained using the gradient vector flow snake.

The use of the watershed algorithm for image segmentation is widespread because it is able to produce a complete division of the image. However, it is susceptible to over-segmentation and in medical image segmentation, this meant that that we do not have good representations of the anatomy. We address this issue by thresholding the gradient magnitude image and performing post-segmentation merging on the initial segmentation map. The automated thresholding technique is based on the histogram of the gradient magnitude map while the post-segmentation merging is based on the similarity in textural features (namely angular second moment, contrast, entropy and inverse difference moment) belonging to two neighboring partitions. When applied to the segmentation of various facial anatomical structures from magnetic resonance (MR) images, the proposed method achieved an overlap index of 92.6% compared to manual contour tracings. It is able to merge more than 80% of the initial partitions, which indicates that a large amount of over-segmentation has been reduced. Results produced using watershed algorithm with and without the proposed and proposed post-segmentation merging are presented for comparisons.

This paper provides an overview of blood flow in the arterial system and aims to estimate the blood velocity from cerebral angiography scans without having acquired data on velocity by using Murray's Law. The estimation technique post-processes the scan and provides crucial 3D visual data for the development of a visualization program of the blood flow in the human brain.

The binding of each intercellular adhesive molecule (ICAM) molecule fragment from Leishmania amazonensis (ICAM-L) to host macrophages was investigated using an indirect immunofluorescent sandwich technique, based on the observation that ICAM-L can block the uptake of L. amazonensis on the macrophage surface and all prepared ICAM-L fragments can react with rabbit anti-ICAM-L antiserum. The ICAM-L fragments lacking the loop 1 (LI) structure failed to bind to macrophages, and the disruption of the LI structure by mercaptoethanol led to the failure of binding. The fragments containing the LI structure functioned similarly to ICAM-L, by temporarily retarding host cell growth and cell cycle progression, and inhibiting the Leishmania infection of host macrophages. These results suggest that LI constitutes the main determinant of the ICAM-L molecule in binding to, and infection of, host macrophages.

We propose a feature-based GVF snake for medical image segmentation here. Feature-based criteria are introduced for the GVF snake to stop its iterations. Without these criteria, the GVF snake might continue its iterations even though it has converged at the targeted object and result in longer computational time. The feature here is the area of the targeted object. Our proposed method comprises of two stages, namely the training stage and the segmentation stage. In the training stage, we acquire prior knowledge on the relative area of the targeted object from training data. In the segmentation stage, the proposed feature-based GVF snake is applied to segment the object from the image after computing the estimated area of the targeted object. In our proposed method, the GVF snake stops its iterations when the area bounded by its propagation is approximately equal to the estimated area and when it undergoes little change over two consecutive iterations. To illustrate the effectiveness of our proposed method, we applied it to the segmentation of the masseter muscle, which is the strongest jaw muscle, from 2-D magnetic resonance (MR) images. Numerical evaluation done indicates good agreement between the computerized and manual segmentations, with mean overlap of 92%.

In this paper, we localize the shape-determinative slices of the masseter, which plays a critical role in the mastication system, from magnetic resonance (MR) data sets for clinical purposes. Shape-based criteria were used to locate the candidates for determinative slices from training data. The localization process involves tracking of the centroid and detecting the locations where the structure of the masseter undergoes an abrupt change in orientation. Having determined all the candidates which satisfy the criteria, fuzzy-c-means (FCM) clustering technique was used to establish the determinative slices. Localization of these slices will facilitate the building of more accurate models. It will also allow for more accurate computerized extraction of the masseter from MR data. In our work here, a hybrid method to shape-based interpolation is used to build the masseter model from magnetic resonance (MR) data sets, and the mean overlap index (¿) achieved is 87.7%. Extraction of the masseter was carried out using our earlier proposed method and the mean ¿ achieved is 8.9%. This indicates good agreement between the results obtained using computerized technique and those contained using manual contour tracing.

Autoimmune thyroiditis (AT) is characterized by a continuous inflammatory self-destructive process that eventually leads to chronic progressive dysfunction of the thyroid. In a previously established experimental AT model, C57bl/6 mice immunized with recombinant mouse thyroid peroxidase (TPO) (rmTPO) developed lymphocytic thyroiditis and anti-TPO antibody but not chronic hypothyroidism. To determine the immunodominant epitope(s) of TPO, T cell proliferation assays were performed in which rmTPO-primed lymph nodes cells were reacted with recombinant mTPO fragments or short overlapping synthetic TPO peptides. Within residue 405-849, peptide 540-559 gave the maximum proliferation response with a stimulation index more than 12. Mice immunized with peptide 540-559 developed antibody against rmTPO and native mouse TPO protein, lymphocytic thyroiditis, and hypothyroidism. In conclusion, this study demonstrated that TPO is the autoantigen for the development of lymphocyte thyroiditis and thyroid dysfunction, and peptide 540-559 is the immunodominant T cell epitope of TPO. Identification of T cell epitopes of TPO may enable the development of immunotherapy to prevent chronic hypothyroidism in AT.

In this paper, we propose a knowledge-driven highly automatic methodology for extracting the masseter from magnetic resonance (MR) data sets for clinical purposes. The masseter is a muscle of mastication which acts to raise the jaw and clench the teeth. In our initial work, we designed a process which allowed us to perform 2-D segmentation of the masseter on 2-D MR images. In the methodology proposed here, we make use of ground truth to first determine the index of the MR slice in which we will carry out 2-D segmentation of the masseter. Having obtained the 2-D segmentation, we will make use of it to determine the region of interest (ROI) of the masseter in the other MR slices belonging to the same data set. The upper and lower thresholds applied to these MR slices, for extraction of the masseter, are determined through the histogram of the 2-D segmented masseter. Visualization of the 3-D masseter is achieved via volume rendering. Our methodology has been applied to five MR data sets. Validation was done by comparing the segmentation results obtained by using our proposed methodology against manual contour tracings, obtaining an average accuracy of 83.5%

Background: Effective pain relief is important after diagnostic and therapeutic arthroscopic knee surgery to permit early discharge and improve comfort and mobility at home. The aim of this study was to assess the efficacy of bupivacaine, ropivacaine, or a combination of ropivacaine, morphine, and ketorolac injected intra-articularly for postoperative pain relief after arthroscopic knee surgery., Methods: Sixty-three healthy patients undergoing knee arthroscopy under local anesthesia (LA) were randomized to receive 1 of the following substances intra-articularly postoperatively: group B: 30 mL of bupivacaine (150 mg); group R: 30 mL of ropivacaine (150 mg); and group RMK: ropivacaine 150 mg, morphine 4 mg, and ketorolac 30 mg in normal saline (total volume 30 mL). Oral paracetamol 1g and tramadol 50 mg were used as rescue drugs. Postoperatively, pain was assessed at rest and movement, and side effects were recorded. The patients were asked to self-assess pain for 7 days and record analgesic consumption as well as activities of daily living (ADLs). Plasma concentration of LA was measured in another 8 patients., Results: All groups had excellent analgesia at 0 and 4 hours postoperatively. Group RMK had significantly lower visual analog pain score at rest at 8 hours and during movement at 8 and 24 hours compared with the other groups (P<.05). Group RMK required less paracetamol and tramadol on day 1 (P<.05), had less sleep disturbances because of pain, more patients were ready to work on days 1 and 2 (P<.05), and were more satisfied on days 1 and 4 to 7. Postoperatively, plasma concentrations of ropivacaine and lidocaine were far below known systemic toxic concentrations in all patients., Conclusion: Addition of morphine and ketolorac to ropivacaine intra-articularly enhances analgesic efficacy of LA, reduces postdischarge analgesic consumption, and improves ADLs without increasing side effects after ambulatory arthroscopic knee surgery.