A perspective on targeting inflammation and cytokine actions in atherosclerosis

Atherosclerosis, a chronic inflammatory disorder of the vasculature that results in cardiovascular disease, continues to pose a significant health and economic burden on modern society. Whilst inflammation has generally been accepted as the key driver of all stages of the disease, it was not until recently that inhibition of a specific proinflammatory cytokine (IL-1β) yielded successful results in the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study trial. This article offers a perspective on targeting inflammation for atherosclerosis, focusing on results of recent Phase III clinical trials, and discusses other potential candidates together with future challenges and prospects

State-of-the-art review and critical success factors for mobile business intelligence

Due to ubiquitous information requirements, market interest in mobile business intelligence (BI) has grown markedly. However, mobile BI market is a relatively new area that has been driven primarily by the IT industry. Yet, there is a lack of systematic study on the critical success factors for mobile BI. This research reviews the state-of-the-art of mobile BI, and explores the critical success factors based on a rigorous examination of the academic and practitioner literature. The study reveals that critical success factors of mobile BI generally fall into four key dimensions, namely security, mobile technology, system content and quality, and organisational support perspectives. The various research findings will be useful to organisations which are considering or undertaking mobile business intelligence initiatives

Chiral microstructures (spirals) fabrication by holographic lithography

We present an optical interference model to create chiral microstructures (spirals) and its realization in photoresist using holographic lithography. The model is based on the interference of six equally-spaced circumpolar linear polarized side beams and a circular polarized central beam. The pitch and separation of the spirals can be varied by changing the angle between the side beams and the central beam. The realization of the model is carried out using the 325 nm line of a He-Cd laser and spirals of sub-micron size are fabricated in photoresist.Comment: 6 page

Do Low Preoperative Vitamin D Levels Reduce the Accuracy of Quick Parathyroid Hormone in Predicting Postthyroidectomy Hypocalcemia?

BACKGROUND: Although some studies have suggested that low preoperative 25-hydroxyvitamin D (25-OHD) levels may increase the risk of hypocalcemia and decrease the accuracy of single quick parathyroid hormone in predicting hypocalcemia after total thyroidectomy, the literature remains scarce and inconsistent. Our study aimed to address these issues. METHODS: Of the 281 consecutive patients who underwent a total/completion total thyroidectomy, 244 (86.8 %) did not require any oral calcium and/or calcitriol supplements (group 1), while 37 (13.2 %) did (group 2) at hospital discharge. 25-OHD level was checked 1 day before surgery, and postoperative quick parathyroid hormone (PTH) was checked at skin closure (PTH-SC). Postoperative serum calcium was checked regularly. Hypocalcemia was defined by the presence of symptoms or adjusted calcium of <1.90 mmol/L. Significant factors for hypocalcemia were determined by univariate and multivariate analyses. The accuracy of PTH-SC in predicting hypocalcemia was measured by area under a receiver operating characteristic curve (AUC), and the AUC of PTH-SC was compared between patients with preoperative 25-OHD <15 and ≥15 ng/mL via bootstrapping. RESULTS: Preoperative 25-OHD level was not significantly different between groups 1 and 2 (13.1 vs. 12.5 ng/mL, p = 0.175). After adjusting for other significant factors, PTH-SC (odds ratio 2.49, 95 % confidence interval 1.52–4.07, p < 0.001) and parathyroid autotransplantation (odds ratio 3.23, 95 % confidence interval 1.22–8.60, p = 0.019) were the two independent factors for hypocalcemia. The AUC of PTH-SC was similar between those with 25-OHD <15 and ≥15 ng/mL (0.880 vs. 0.850, p = 0.61) CONCLUSIONS: Low 25-OHD was not a significant factor for hypocalcemia and did not lower the accuracy of quick PTH in predicting postthyroidectomy hypocalcemia

Exogenous Expression of Human apoA-I Enhances Cardiac Differentiation of Pluripotent Stem Cells

The cardioprotective effects of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA-I) are well documented, but their effects in the direction of the cardiac differentiation of embryonic stem cells are unknown. We evaluated the effects of exogenous apoA-I expression on cardiac differentiation of ESCs and maturation of ESC-derived cardiomyocytes. We stably over-expressed full-length human apoA-I cDNA with lentivirus (LV)-mediated gene transfer in undifferentiated mouse ESCs and human induced pluripotent stem cells. Upon cardiac differentiation, we observed a significantly higher percentage of beating embryoid bodies, an increased number of cardiomyocytes as determined by flow cytometry, and expression of cardiac markers including α-myosin heavy chain, β-myosin heavy chain and myosin light chain 2 ventricular transcripts in LV-apoA-I transduced ESCs compared with control (LV-GFP). In the presence of noggin, a BMP4 antagonist, activation of BMP4-SMAD signaling cascade in apoA-I transduced ESCs completely abolished the apoA-I stimulated cardiac differentiation. Furthermore, co-application of recombinant apoA-I and BMP4 synergistically increased the percentage of beating EBs derived from untransduced D3 ESCs. These together suggests that that pro-cardiogenic apoA-I is mediated via the BMP4-SMAD signaling pathway. Functionally, cardiomyocytes derived from the apoA-I-transduced cells exhibited improved calcium handling properties in both non-caffeine and caffeine-induced calcium transient, suggesting that apoA-I plays a role in enhancing cardiac maturation. This increased cardiac differentiation and maturation has also been observed in human iPSCs, providing further evidence of the beneficial effects of apoA-I in promoting cardiac differentiation. In Conclusion, we present novel experimental evidence that apoA-I enhances cardiac differentiation of ESCs and iPSCs and promotes maturation of the calcium handling property of ESC-derived cardiomyocytes via the BMP4/SMAD signaling pathway

A non-invasive biomechanical device to quantify knee rotational laxity: Verification of the device in human cadaveric specimens

Background: Biomechanical measurement tools have been developed and widely used to precisely quantify knee anterior-posterior laxity after anterior cruciate ligament (ACL) injury. However, validated objective device to document knee rotational laxity, though being developed by different researchers, are not yet widely used in the daily clinical practice. A new biomechanical device was developed to quantify knee internal and external rotations. Methods: The reliability of the new biomechanical device which measures knee rotations were tested. Different torques (1-10Nm) were applied by the device to internally and externally rotate human cadaveric knees, which were held in a flexion angle of 30 . The rotations were measured by the device in degrees. There were two independent testers, and each tester carried out three trials. Intra-rater and inter-rater reliability were quantified in terms of intraclass correlation (ICC) coefficient among trials and between testers. The device was verified by the comparison with a computer assisted navigation system. ICC was measured. Mean, standard deviation and 95% confident interval of the difference as well as the root mean square difference were calculated. The correlations were deemed to be reliable if the ICC was above 0.75. Results: The intra-rater and inter-rater reliability achieved high correlation for both internal and external rotation, ranged from 0.959 to 0.992. ICC between the proposed meter and the navigation system for both internal and external rotation was 0.78. The mean differences were 2.3 and 2.5 for internal and external rotation respectively. Conclusions: A new knee rotational laxity meter was proposed in this study. Its reliability was verified by showing high correlation among trials. It also showed good correlation to a gold standard of measurement. It might be used to document knee rotational laxity for various purposes, especially after ACL injury, after further validation of the device in human subject

Influence of Maternal Infection and Pregnancy Complications on Cord Blood Telomere Length

BACKGROUND: Exposure to suboptimal intrauterine environment might induce structural and functional changes that can affect neonatal health. Telomere length as an important indicator of cellular health has been associated with increased risk for disease development. OBJECTIVES: This study was aimed to examine the independent and combined effects of maternal, obstetric, and foetal factors on cord blood telomere length (TL). METHODS: Pregnant women at the gestational age of 20th to 24th week who attended the antenatal clinic of a major local hospital in Hong Kong were recruited. Participants were asked to complete a questionnaire on demographics, health-related quality of life, and history of risk behaviors. Medical history including pregnancy complications and neonatal outcomes was obtained from electronic medical records of both mother and neonate. Umbilical cord blood was collected at delivery for TL determination. RESULTS: A total of 753 pregnant women (average age: 32:18 ± 4:51 years) were recruited. The prevalence of maternal infection, anaemia, and hypertension during pregnancy was 30.8%, 30.0%, and 6.0%, respectively. The adjusted regression model displayed that maternal infection was negatively associated with cord blood TL (β = −0:18, p = 0:026). This association became even stronger in the presence of antenatal anaemia, hypertension, delivery complications, or neonatal jaundice (β = −0:25 to −0.45). Conclusions. This study consolidates evidence on the impact of adverse intrauterine environment at the cellular level. Maternal infection was significantly associated with shorter cord blood TL in a unique manner such that its presence may critically determine the susceptibility of telomere to other factors

Oral health of community dwelling elders in Hong Kong

Introduction: The world’s population is ageing and the elders are vulnerable to oral health problems. This project aimed to observe the oral health status of community dwelling elders in Hong Kong, investigate the oral health impact on their quality of life and nutritional status, and provide oral health education and preventive service. Methods: Community dwelling elders (65 or above) were recruited from five community centers. An interviewer-administered questionnaire was completed to collect information on their socio-demographic background and oral health perception/practice. Their oral health related quality of life (OHQoL) and nutritional status were measured by using the Geriatric Oral Health Assessment Index (GOHAI) and Mini-Nutritional Assessment (MNA), respectively. Their tooth and periodontal status, oral hygiene and soft tissues were examined. Individualized advice, oral health education and scaling were provided. Results: A total of 195 elders participated. Despite their sound knowledge on dental caries, their awareness of the causes and risk factors of periodontal diseases was low. Several misconceptions of oral health were common and their expectation towards oral health was low. Although 81% brush their teeth at least twice a day, over 75% did not perform interdental cleaning mainly due to unawareness of the necessity (32%) and lack of skills (42%). Their dental visits were treatment-driven and mainly for pain-relieving and emergency care. Only 19% were regular dental attendees. The mean (SD) DMFT was 8.9 (7.8). Over 60% had periodontal pockets; 6% were edentulous and 38% had fewer than 20 teeth. The mean (SD) total GOHAI score was 56.4 (8.0); 60% reported negative impact of oral health on their quality of life. The mean (SD) MNA score was 25.2 (2.9); 30% had malnutrition or were at risk. Multivariate analysis showed that tooth loss and untreated decayed teeth (DT) were significant determinants of poor OHQoL; older age, higher education level, and poorer OHQoL were significantly associated with higher risk of malnutrition (all p<0.05). Conclusions: Oral health problems are common among community dwelling elders in Hong Kong. Their oral health awareness and practice are yet to be improved. Tooth loss and unmet treatment need for dental caries significantly compromise elders’ quality of life, which in turn increases their risk for malnutrition. Outreach oral health education and service are well received by the community.published_or_final_versio

The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways

Atherosclerosis, a chronic inflammatory disorder of the walls of arteries, causes more deaths worldwide than any other disease. Cytokines, which are present at high levels in atherosclerotic plaques, play important roles in regulating the initiation and the progression of the disease. Previous studies using animal and cell culture model systems revealed protective, anti-atherogenic effects of the cytokine interleukin-33 (IL-33). The action of this cytokine involves both the induction and suppression of expression of many genes. Unfortunately, the signaling pathways that are responsible for the inhibition of gene expression by this cytokine are poorly understood. Further studies are required given the important roles of genes whose expression is inhibited by IL-33 in key cellular processes associated with atherosclerosis such as monocyte recruitment, foam cell formation and lipoprotein metabolism. We have investigated here the roles of various known IL-33 activated signaling pathways in such inhibitory actions using RNA interference-mediated knockdown assays and monocyte chemotactic protein-1 and intercellular adhesion molecule-1 as model genes. Key roles were identified for extracellular signal-regulated kinase-1/2, p38α kinase, c-Jun N-terminal kinase-1/2, phosphoinositide 3-kinase-γ, and p50 and p65 nuclear factor-κB in such inhibitory action of IL-33. These studies provide new insights on the signaling pathways through which IL-33 inhibits the macrophage expression of key atherosclerosis-associated genes