Cardiovascular risk prediction with cardio-ankle vascular index in the malaysian cohort study.

The cardio-ankle vascular index (CAVI) is an important parameter assessing arterial function. It reflects arterial stiffness from the origin of the aorta to the ankle, and the algorithm is blood pressure independent. Recent data have suggested that a high CAVI score can predict future cardiovascular disease (CVD) events; however, to date, no study has been done in Malaysia. We conducted a prospective study on 2,168 The Malaysian Cohort (TMC) CVD-free participants (971 men and 1,197 women; mean age 51.64 ± 8.38 years old) recruited from November 2011 to March 2012. This participants were followed-up until the emergence of CVD incidence and mortality (endpoint between May to September 2019; duration of 7.5 years). Eligible participants were assessed based on CAVI baseline measurement which categorised them into low (CAVI <9.0) and high (CAVI ≥ 9.0) scores. The CVD events in the group with high CAVI (6.5 %) were significantly higher than in the low CAVI (2.6 %) group (p < 0.05). CAVI with cut-off point ≥ 9.0 was a significant independent predictor for CVD event even after adjustment for male, ethnicity, age, and intermediate atherogenic index of plasma (AIP). Those who have higher CAVI have 78 % significantly higher risk of developing CVD compared to those with the low CAVI (adjusted OR [95 % CI] = 1.78 [1.04 - 3.05], p =0.035). In addition, the participants with higher CAVI have significantly lower survival probability than those who have lower CAVI values. Thus, this study indicated that the CAVI can predict CVD event independently among the TMC participants.

Discordance between Fasting Plasma Glucose (FPG) and HbA1c in Diagnosing Diabetes and Pre-diabetes in The Malaysian Cohort.

OBJECTIVE: In this present study, we aim to evaluate the accuracy of the HbA1c relative to fasting plasma glucose (FPG) in the diagnosis of diabetes and pre-diabetes among The Malaysian Cohort (TMC) participants. METHODOLOGY: FPG and HbA1c were taken from 40,667 eligible TMC participants that have no previous history of diabetes, aged between 35-70 years and were recruited from 2006 - 2012. Participants were classified as normal, diabetes and pre-diabetes based on the 2006 World Health Organization (WHO) criteria. Statistical analyses were performed using ANOVA and Chi-square test, while Pearson correlation and Cohen's kappa were used to examine the concordance rate between FPG and HbA1c. RESULTS: The study samples consisted of 16,224 men and 24,443 women. The prevalence of diabetes among the participants was 5.7% and 7.5% according to the FPG and HbA1c level, respectively. Based on FPG, 10.6% of the participants had pre-diabetes but this increased to 14.2% based on HbA1c (r=0.86; P<0.001). HbA1c had a sensitivity of 58.20 (95% CI: 56.43, 59.96) and a specificity of 98.59 (95% CI: 98.46, 98.70). CONCLUSION: A higher prevalence of pre-diabetes and diabetes was observed when using HbA1c as a diagnosis tool, suggesting that it could possibly be more useful for early detection. However, given that HbA1c may also have lower sensitivity and higher false positive rate, several diagnostic criteria should be used to diagnose diabetes accurately.

Diagnostic accuracy of periapical radiograph, cone beam computed tomography, and intrasurgical linear measurement techniques for assessing furcation defects: a longitudinal randomised controlled trial.

OBJECTIVES: The aim of this study was to evaluate the accuracy of cone beam computed tomography (CBCT), periapical radiograph, and intrasurgical linear measurements in the assessment of molars with furcation defects. MATERIALS AND METHODS: This parallel, single-blinded, randomised controlled trial (RCT) consisted of 22 periodontitis patients who had molar with advanced furcation involvement (FI). All patients followed the same inclusion criteria and were treated following the same protocol, except for radiographic evaluation (CBCT vs. periapical). This study proposed and evaluated five parameters that represent the extent and severity of furcation defects in molars teeth, including CEJ-BD (clinical attachment loss), BL-H (depth), BL-V (height), RT (root trunk), and FW (width). RESULTS: There were no statistically significant differences between CBCT and intrasurgical linear measurements for any clinical parameter (p > 0.05). However, there were statistically significant differences in BL-V measurements (p < 0.05) between periapical and intrasurgical measurements in maxillary molars. Meanwhile, the sensitivity were 62.8% and 56.9% for CBCT and periapical, respectively. CONCLUSIONS: Overall, when compared to the intrasurgical measurements, CBCT provided better diagnostic, sensitivity, and quantitative information on CAL, height, depth, and width of the furcation defects than periapical radiograph. CLINICAL RELEVANCE: An accurate presurgical furcation diagnostic can guide the clinicians from the stage of diagnosis to definitive management so that unnecessary periodontal surgical interventions can be prevented.

The accuracy of linear measurements in cone beam computed tomography for assessing intrabony and furcation defects: a systematic review and meta-analysis / La precisión de las mediciones lineales en la tomografía computarizada de haz cónico para evaluar defectos intraóseos y de furcación: una revisión sistemática y un metanálisis

Objective: This study aims to assess the accuracy of the linear measurements of intrabony and/or furcation defect quantified by cone beam computed tomography (CBCT). Material and Methods: A systematic search of the literature was conducted by two authors independently from the PubMed, Scopus, and EBSCO for full articles published in journals between January 2003 and March 2017. Eligible studies were assessed for quality and heterogeneity using the QUADAS-2 tool. A meta-analysis was performed to identify the accuracy of CBCT in the measurement of intrabony defects. The effect size was estimated and reported as the standardised mean difference (SMD). Results: A total of 105 titles and abstracts were screened. Of those, 11 articles met the inclusion criteria for the systematic review while only four were selected for meta-analysis. The overall effects of standardized mean difference and 95% CI was -0.03 [95% CI -0.67 to 0.60] with a x2 statistic of 0.49 with 3 degrees of freedom (p>0.05), I2= 0.01%. Conclusion: CBCT is highly accurate and reproducible regarding linear measurements for assessing intrabony defects with a weighted standardized mean difference of 0.03 mm. More randomised controlled trials are required to assess the accuracy of CBCT in assessing patients with periodontal defects.

Objetivo: Este estudio tiene como objetivo evaluar la precisión de las mediciones lineales de defectos intraóseos y/o de furcación cuantificados por tomografía computarizada de haz cónico (CBCT). Material y Métodos: Dos autores, independientemente realizaron una búsqueda sistemática de la literatura en PubMed, Scopus y EBSCO, para obtener artículos completos publicados en revistas entre Enero de 2003 y Marzo de 2017. Los estudios elegibles se evaluaron para determinar la calidad y la heterogeneidad utilizando la herramienta QUADAS-2. Se realizó un metanálisis para identificar la precisión de CBCT en la medición de defectos intraóseos. El tamaño del efecto se estimó y se informó como la diferencia de medias estandarizada (DME). Resultados: Se seleccionaron un total de 105 títulos y resúmenes. De ellos, 11 artículos cumplieron con los criterios de inclusión para la revisión sistemática, mientras que solo cuatro fueron seleccionados para el metanálisis. Los efectos generales de la diferencia de medias estandarizada y el IC del 95% fueron -0.03 [IC del 95%: -0.67 a 0.60] con una estadística X2 de 0.49 con 3 grados de libertad (p>0.05), I2= 0.01%. Conclusión: CBCT es altamente preciso y reproducible con respecto a mediciones lineales para evaluar defectos intraóseos con una diferencia de medias estandarizada ponderada de 0.03 mm. Se requieren más ensayos controlados aleatorios para evaluar la precisión de CBCT en la evaluación de pacientes con defectos periodontales.

Nucleofection optimization and in vitro anti-tumourigenic effect of TRAIL-expressing human adipose-derived mesenchymal stromal cells.

BACKGROUND: Tumour homing capacity of engineered human adipose-derived mesenchymal stromal cells (ADMSCs) expressing anti-tumour agents might be the key for a much safer and yet efficient targeted tumour therapy. However, ADMSCs exhibit resistant to most gene transfection techniques and the use of highly efficient viral vectors has several disadvantages primarily concerning safety risk. Here, we optimized the use of highly efficient and safe nucleofection-based transfection using plasmid encoded for TNF-Related Apoptosis Inducing Ligand (TRAIL) into ADMSCs and investigated the potential anti-tumourigenic of TRAIL-expressing ADMSCs (ADMSCs-TRAIL) on selected cancer models in vitro. METHODS: Different concentration of TRAIL-encoded plasmid and ADMSCs were nucleofected and the percentage of fluorescence cells were analyzed to determine the optimal condition. TRAIL protein and mRNA were validated in nucloeofected ADMSCs using ELISA and RT-PCR respectively. Evaluation of TRAIL specific death receptors were performed on both tumours (A549/lung tumour, LN18/glioblastoma and HepG2/hepatocellular carcinoma) and haematological malignant lines (REH/acute lymphocytic leukaemia, K562/chronic myelogenous leukaemia and KMS-28BM/multiple myeloma) using flow cytometry. ADMSCs-TRAIL was subsequently assessed for anti-tumourigenic properties using both proliferation assay (MTS assay) and apoptosis assay (Annexin-V / Propidium Iodide staining). RESULTS: Nucleofection showed increased total plasmid concentration (2 µg to 8 µg) resulted in significantly higher reporter expression (11.33% to 39.7%) with slight reduction on cells viability (~10%). ADMSCs-TRAIL significantly inhibited ~50% of cell proliferation in LN18, signifying sensitivity of the cell to ADMSCs-TRAIL mediated inhibition. Inhibition of both tumour and malignant lines proliferation by ADMSCs-TRAIL conditioned medium noticed in HepG2, A549 and REH respectively, whereas K562 and KMS-28BM malignant lines exhibit resistant to ADMSCs-TRAIL mediated inhibition. Moreover, we found that native ADMSCs alone were capable of inducing apoptosis in both LN18 and HepG2 tumour lines, despite substantial increased on the percentage of apoptosis by ADMSCs-TRAIL. CONCLUSION: ADMSCs-TRAIL selectively inhibit cancer model and markedly induces apoptosis. Through investigation of the specific TRAIL death receptors expression, we saw that the receptors expression did influence the sensitivity of some but not all cancer lines to TRAIL-mediated inhibition. This study provides further insight into the anti-tumourigenic potential of ADMSCs-TRAIL on different cancer models.

Comparative cellular and molecular analyses of pooled bone marrow multipotent mesenchymal stromal cells during continuous passaging and after successive cryopreservation.

The clinical application of human bone marrow derived multipotent mesenchymal stromal cells (MSC) requires expansion, cryopreservation, and transportation from the laboratory to the site of cell implantation. The cryopreservation and thawing process of MSCs may have important effects on the viability, growth characteristics and functionality of these cells both in vitro and in vivo. More importantly, MSCs after two rounds of cryopreservation have not been as well characterized as fresh MSCs from the transplantation perspective. The objective of this study was to determine if the effect of successive cryopreservation of pooled MSCs during the exponential growth phase could impair their morphology, phenotype, gene expression, and differentiation capabilities. MSCs cryopreserved at passage 3 (cell bank) were thawed and expanded up to passage 4 and cryopreserved for the second time. These cells (passive) were then thawed and cultured up to passage 6, and, at each passage MSCs were characterized. As control, pooled passage 3 cells (active) after one round of cryopreservation were taken all the way to passage 6 without cryopreservation. We determined the growth rate of MSCs for both culture conditions in terms of population doubling number (PDN) and population doubling time (PDT). Gene expression profiles for pluripotency markers and tissue specific markers corresponding to neuroectoderm, mesoderm and endoderm lineages were also analyzed for active and passive cultures of MSC. The results show that in both culture conditions, MSCs exhibited similar growth properties, phenotypes and gene expression patterns as well as similar differentiation potential to osteo-, chondro-, and adipo-lineages in vitro. To conclude, it appears that successive or multiple rounds of cryopreservation of MSCs did not alter the fundamental characteristics of these cells and may be used for clinical therapy.