Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease.

BACKGROUND: Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH). OBJECTIVES: 1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial. DESIGN: A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period. SETTING: Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. PARTICIPANTS: A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers). MEASUREMENTS: A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group. RESULTS: Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH. CONCLUSION: These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.

Evaluation of Graft Maturation by MRI in Anterior Cruciate Ligament Reconstruction With and Without Concomitant Anterolateral Ligament Reconstruction.

Background: Single-bundle anterior cruciate ligament reconstruction (SB-ACLR) with concomitant anterolateral ligament reconstruction (ALLR) has been associated with better clinical results when compared with isolated SB-ACLR. However, it is not known whether the improved outcomes are the result of the influence of concomitant ALLR on ACL graft healing. Purpose/Hypothesis: The purpose of this study was to determine whether concomitant ALLR is associated with improved graft ligamentization after SB-ACLR. It was hypothesized that ALLR would not affect graft healing. Study Design: Cohort study; Level of evidence, 3. Methods: A 1 to 1 matching study was conducted on a consecutive series of 732 patients who underwent ACLR using a hamstring tendon autograft between 2007 and 2019. Patients were excluded if they had skeletal immaturity, inflammatory joint disease, multiple ligament reconstruction (other than ALLR), or a graft rupture. Patients with concomitant SB-ACLR and ALLR (SB-ACLR/ALLR) and isolated SB-ACLR were matched 1 to 1 based on age, sex, examination under anesthesia (EUA) grade 3 pivot shift, EUA grade 3 anterior drawer test, presence of graft impingement, sagittal graft angle, skeletal maturity, lack of generalized ligamentous laxity, and multiple ligamentous injury. A total of 40 matched pairs underwent postoperative magnetic resonance imaging (MRI) within the second year after surgery to assess graft ligamentization, which was measured by the signal-to-noise quotient (SNQ) of the ACL graft. Results: The mean follow-up period was 41 months, with a 2-year follow-up rate of 80% in the SB-ACLR/ALLR group and 98% in the isolated SB-ACLR group. The mean duration between the index operation and MRI was 16.4 ± 3.4 months. No significant difference was observed in the SNQ of the ACL graft between the SB-ACLR/ALLR and SB-ACLR groups (6.9 ± 4.6 vs 5.2 ± 4.8, respectively; P = .066). Conclusion: Study findings indicated that a concomitant ALLR at the time of hamstring tendon autograft ACLR did not affect graft healing as assessed by the SNQ of the ACL graft.

Differences in Clinical Outcomes Between Patients With Retear After Supraspinatus Tendon Repair and Those With Intact Repair at 5-Year Follow-up.

BACKGROUND: It is well known that rotator cuff repair is associated with an overall retear rate of 21% to 26%. However, a cuff retear may not necessarily be associated with poor clinical outcomes. HYPOTHESIS: There would be no difference in clinical outcomes between patients with a cuff retear and those with an intact repair at a midterm follow-up of 5 years. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective study was conducted involving patients who received arthroscopic complete repair of the supraspinatus tendon between January 2009 and December 2017. Patients who did not have a postoperative magnetic resonance imaging (MRI) scan or who had a follow-up of <5 years were excluded. Clinical outcomes, including the visual analog scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, and active forward flexion (FF) of the involved shoulder were assessed at the 2-year and 5-year follow-up points. RESULTS: The study group included 105 patients with a mean follow-up of 85 months. MRI scans were performed at a mean of 20 months. Fourteen full-thickness cuff retears and 91 intact repairs were identified using postoperative MRI scans. Significant improvement in VAS score, ASES score, and FF were found between the preoperative assessment and the 2 designated follow-up points (2 years and 5 years) in both the cuff retear and the intact repair groups (P < .001). The VAS and ASES scores at the 2-year follow-up for the intact repair group were 1.8 ± 2.0 and 80.7 ± 18.1, respectively. The corresponding values for the retear group were 2.3 ± 2.2 and 71.9 ± 19.5, respectively. No significant difference was found between the 2 groups in the VAS and ASES scores at the 2-year follow-up. However, patients with an intact repair had a better VAS score (1.4 ± 1.8; P = .049) and ASES score (81.7 ± 17; P = .019) than those with a cuff retear at the 5-year assessment (3.0 ± 2.8 and 67.1 ± 22.9, respectively). In the intact repair group, 91% of patients achieved the minimal clinically important difference for the 5-year VAS score, compared with 54% in the cuff retear group (P < .001). The corresponding values for the 5-year ASES score were 80% and 54%, respectively (P = .044). FF measurements at the 5-year follow-up in patients with intact repair and those with a cuff retear were 161°± 23° and 144°± 37°, respectively (P = .059). Continuous improvement in VAS score and FF between the 2-year and 5-year follow-up was observed in the intact repair group (P = .005 and P = .04, respectively). CONCLUSION: The patients with an intact repair had better VAS and ASES scores compared with those who had a cuff retear at a midterm follow-up of 5 years. Between the 2-year and the 5-year follow-up, some further improvement was observed in the VAS score and FF in the intact repair group.

Smokers Achieved Minimal Clinically Important Difference for Visual Analog Scale and American Shoulder and Elbow Surgeons Scores at a Lower Rate Than Nonsmokers Even When Repaired Supraspinatus Tendons Were Intact on Postoperative Magnetic Resonance Imaging.

Purpose: To investigate the impact of smoking on clinical outcomes after repair of supraspinatus tendon in patients who had an intact repair found on postoperative magnetic resonance imaging. Methods: Patients who received primary complete repair of supraspinatus tendon tear between 2014 and 2020 were retrospectively identified. Patients were excluded if a postoperative magnetic resonance imaging scan was not available or if the follow-up was less than 2 years. Visual analog score (VAS), American Shoulder and Elbow Surgeons (ASES) score, and active forward flexion were assessed at the 2-year follow-up. The percentage of patients acquiring minimal clinically important difference (MCID) was reported. Results: One hundred primary supraspinatus tendon repairs were included. The healing rate was 77% in smokers and 90% in nonsmokers. Smoking was the independent predictor of a poorer 2-year VAS (P < .001) and ASES (P < .001) scores. Significant improvement in clinical outcomes was observed between preoperation and the 2-year follow-up, regardless of the integrity of the repair or smoking status (P < .001). When the repaired tendon was intact, nonsmokers had a greater chance of achieving MCID in 2-year VAS and ASES scores than smokers. Ninety-nine percent of nonsmokers, compared with 82% of smokers, achieved MCID in VAS at the 2-year follow-up (P = .023). The corresponding figures for ASES were 98% and 71%, respectively (P = .004). Conclusions: In this study, smoking was associated with poorer clinical outcomes, including a greater 2-year VAS pain score and a lower 2-year ASES score, when compared with nonsmokers, even in cases in which there was no full-thickness retear of the repaired supraspinatus tendon. Level of Evidence: Level III, retrospective cohort study.

Repair of meniscus root tear - Is there a difference between medial meniscus root repair and lateral meniscus root repair? A systematic review and meta-analysis.

PURPOSE: Complete meniscus root tear is associated with meniscus extrusion; this causes a loss of meniscus function and accelerated osteoarthritis of the knee. Existing small-scale retrospective case-control studies suggested that the outcomes were different between medial and lateral meniscus root repair. This meta-analysis aims to study whether such discrepancies exist via a systematic review of the available evidence in the literature. METHODS: Studies evaluating the outcomes of surgical repair of posterior meniscus root tears, with reassessment MRI or second-look arthroscopy, were identified through a systematic search of PubMed, Embase, and Cochrane Library. The degree of meniscus extrusion, healing status of the repaired meniscus root, and functional outcome scores after repair were the outcomes of interest. RESULTS: Among the 732 studies identified, 20 studies were included in this systematic review. 624 knees and 122 knees underwent MMPRT and LMPRT repair, respectively. The amount of meniscus extrusion following MMPRT repair was 3.8 ± 1.7 mm, which was significantly larger than the 0.9 ± 1.2 mm observed after LMPRT repair (p < 0.001). Significantly better healing outcomes were observed on reassessment MRI after LMPRT repair (p < 0.001). The postoperative Lysholm score and IKDC score was also significantly better after LMPRT than MMPRT repair (p < 0.001). CONCLUSIONS: LMPRT repairs resulted in significantly less meniscus extrusion, substantially better healing outcomes on MRI, and superior Lysholm/IKDC scores, when compared to MMPRT repair. This is the first meta-analysis we are aware of that systematically reviews the differences in the clinical, radiographic, and arthroscopic results of MMPRT and LMPRT repair.

Evaluation of Graft Ligamentization by MRI After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: The tendon graft used in anterior cruciate ligament reconstruction (ACLR) undergoes "ligamentization" after implantation, and the reported length of this process varies from 6 to 48 months. Some grafts have ruptured at subsequent follow-up evaluations. Although the progress of graft ligamentization can be followed with postoperative magnetic resonance imaging (MRI) for reassessment, it is not known whether a delay in ligamentization (as reflected by a higher signal of the graft) is associated with an increased chance of subsequent graft rupture. HYPOTHESIS: Signal intensity of the graft on reassessment MRI (signal-noise quotient [SNQ]) would be associated with the incidence of future graft rupture at subsequent follow-up. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 565 ACLRs with intact graft on first-time reassessment MRI after surgery were followed for a mean period of 67 months. The rates of 1-year and 2-year follow-up were 99.5% and 84.5%, respectively. The signal intensity of the intact graft on the first-time reassessment MRI was evaluated (1) quantitatively by the SNQ and (2) qualitatively with the modified Ahn classification. Among the 565 ACLRs, 23 additional graft ruptures developed during a time interval of 7 months to 9 years after the surgery. RESULTS: Higher SNQ was associated with increased chance of subsequent graft rupture (SNQ 7.3 ± 6 for subsequent graft rupture vs 4.4 ± 4 for grafts without subsequent rupture; P = .004, Mann-Whitney U test). The other important confounders that were associated with increased chance of graft rupture were younger age at the time of ACLR (P < .001) and longer follow-up time (P = .002). Multiple linear regression showed that all 3 factors (higher SNQ, younger age, and longer follow-up) were independent predictors of graft rupture (SNQ, P = .03; age, P < .001; follow-up, P = .012). When the reassessment MRI was performed in the second year after ACLR, the odds ratio of future graft rupture of a heterogeneous hyperintense graft when compared with a homogeneous hypointense graft was 12.1 (95% CI = 2.8 to 52.6) P < .001, Fisher exact test). CONCLUSION: Higher signal intensity of the intact graft on reassessment MRI (higher SNQ and heterogeneous hyperintense graft) was associated with increased chance of subsequent graft rupture.

Association of Smoking With Graft Rupture After Anterior Cruciate Ligament Reconstruction.

Background: The effect of smoking on graft rupture after anterior cruciate ligament (ACL) reconstruction is not well understood. Hypothesis: It was hypothesized that there will be no relationship between tobacco use and graft rupture after ACL reconstruction, as reflected by postoperative magnetic resonance imaging (MRI) and arthroscopic examination. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 233 patients who received primary ACL reconstruction with hamstring tendon autograft between January 1, 2013, and December 31, 2019, and who underwent MRI evaluation at 20.2 ± 1.9 months postoperatively. The patients were categorized by smoking history into 2 groups: 39 smokers and 194 nonsmokers. The 2 groups did not differ significantly in age, sex, operative technique, preinjury Tegner score, or mean time until postoperative MRI. The primary outcome was graft rupture rate, with rupture confirmed by either arthroscopic assessment or postoperative MRI diagnosis. The secondary outcome measure was degree of graft ligamentization, evaluated by measuring the signal-to-noise quotient (SNQ) of the graft. Results: The overall ACL graft rupture rate was 6.0%. The rupture rate was significantly higher in smokers than in nonsmokers (12.8% vs 4.6%, respectively; P = .0498). Smokers also had a significantly higher whole-graft SNQ compared with nonsmokers (4.7 ± 4.4 vs 3.3 ± 3.7, respectively; P = .028), suggesting less satisfactory ligamentization in smokers. Conclusion: Smoking was associated with a higher risk of graft rupture of ACL reconstruction and a higher SNQ of the intact graft as shown on postoperative MRI.

Outcomes and Impact of Fragility Fracture among Geriatrics Patients who Underwent Hip Surgery in Hospital Kuala Lumpur.

Introduction: Fragility fractures are common in the elderly. It is associated with increased mortality, reduced mobility, and poorer quality of life. In addition, post-operative functional outcomes are limited locally. Materials and methods: A cross-sectional phone interview was conducted with elderly patients who underwent hip surgery or their caregivers between March 2019 and Feb 2020, at least six months after the operation. Results: A total of 137 cases were approached, and 77 subjects completed the interview (58.4%), among which 54/77 (70.1%) were female, and 66/77 (85.7%) were caregivers. The proportion of subjects who could ambulate independently dropped from 66/77, prior to fracture, to 17/77 post-surgery. We noted a significant deterioration in the modified Barthel Index from the median of 100 (IQR = 0) to 91 (IQR 25.5; p <0.001). There was also a significant decline in the self-perceived physical strength of 30% (IQR 30, p <0.001); and in the functionality of 35% (IQR40; p <0.001). A total of 48/77 (62.3%) returned to their original residence, while 5 cases (6.5%) were institutionalised, and 14/77 (18.2%) died prior to the survey. Thirty-six subjects reported additional costs in the care of patients, ranging from RM100 to RM6000 (USD25 to USD1450) per month. Conclusion: Decline in physical and functional status is closely related to the quality of life as the majority reported a poorer health status after the fracture. Although this study is limited by the small sample size, it provided insights into patients' experiences and household burdens. Hence, well-coordinated services and monitoring are important for better outcomes.

mHealth in hyper-connected Hong Kong: examining attitudes and access to mobile devices and health information among older Chinese residents.

BACKGROUND: Hong Kong Special Administrative Region is one of the most technologically advanced and interconnected cities in the world in terms of ownership of internet-enabled mobile devices. mHealth programs that make use of mobile devices such as smart phones and tablets to maximise access to health information, have been identified as having great potential for ageing communities for the management of health and social care needs. This paper reports the findings of a two-stage exploratory research project which examined the experiences and perceptions of Hong Kong residents aged over 60 years in relation to mHealth technologies and health literacy. METHODS: This study collected data from older Hong Kong residents at a community centre. Data were collected at two stages in July and August 2019. Stage one involved a one-on-one interview at Centre A with each research participant. The self-report surveys included seven questions about mobile phone ownership and a 16-item gerontechnology survey previously used in Hong Kong. Stage two of the data collection involved three discussion groups with the research participants that were run over a 3-week period. RESULTS: (I) Providing health information via digital devices was considered promising and acceptable by most of our participants. (II) Major concerns that impeded the elders' use of digital devices were their lack of the necessary skills to use these gadgets and their loss of memory. (III) Many participants stated their concern that they found it difficult to recall information immediately after being taught. (IV) Most participants had problems in reading because of low literacy levels or some age-related eye-diseases. (V) Video instructions were preferred by participants as audio and visual input is more useful than rather than static written information with heavy reading requirements. CONCLUSIONS: Participants were interested in using mHealth technologies. Education and ongoing support in their use is necessary.

Alendronate use in older patients with reduced renal function: challenges and opportunities in clinical practice.

In this retrospective cohort study, alendronate use among older osteoporosis patients (age>65 years) with reduced renal function (creatinine clearance<35ml/min) was not associated with significant deterioration in renal function from baseline nor increased incidence of osteoporotic fractures or acute kidney injury, compared with patients conservatively managed with only calcium/vitamin D supplementation. INTRODUCTION: Oral bisphosphonates are not recommended in patients with creatinine clearance (CrCl) <35ml/min, although this is not supported by post hoc analyses of pivotal oral bisphosphonate studies. As both osteoporosis and renal insufficiency are more prevalent with advancing age, it is important to determine the safety and efficacy of oral bisphosphonates among these patients. METHODS: Patients with CrCl <35ml/min on alendronate (group A, n=98), with CrCl <35ml/min conservatively managed (group B, n=96), and with CrCl ≥35ml/min on alendronate (group C, n=96) were followed up to 22 months. Primary outcomes were mean change in CrCl from baseline in group A compared with groups B and C, respectively. Secondary outcomes were the incidence of osteoporotic fractures and adverse events between groups. RESULTS: There was no significant change in CrCl from baseline when comparing group A (-1.53±6.83ml/min) with group B (0.59±5.17ml/min) (p=0.075), and group A with group C (-3.71±7.54ml/min) (p=0.163). There was no significant increase in incidences of osteoporotic fractures in group A compared with group B (adjusted relative risk (aRR) 2.02, 95% confidence interval (CI) 0.64-6.37) and group A compared with group C (aRR 1.15, 95% CI 0.46-2.89). There was no significant difference in incidences of acute kidney injury (AKI) in group A compared with group B (aRR 0.48, 95% CI 0.20-1.12). Although statistically non-significant, there was an increase in AKI incidence in group A compared with group C (RR 7.84, 95% CI 0.98-62.66). CONCLUSION: Among patients with CrCl <35ml/min, alendronate therapy was not associated with significant deterioration in renal function from baseline. Although not powered for secondary outcomes, there were no statistically significant differences in osteoporotic fracture or AKI incidence between the groups.

Effects of Senior Simulation Suit Programme on nursing students' attitudes towards older adults: A randomized controlled trial.

BACKGROUND: As populations age worldwide, nursing educational institutions need to train nurses not only to provide health care services specific to the elderly, but also to have a positive attitude as they work. The present study aimed to investigate the efficacy of a Senior Simulation Suit Programme (SSSP). The SSSP, which focused on mimicking the physiological experiences of an 80 year-old person, was hypothesized to increase the wearer's positive attitude towards older adult care. METHODS: A single-blinded, randomized controlled trial was used to evaluate the efficacies of SSSP. One hundred and thirty-nine (139) nursing students were randomly assigned to either SSSP group (n = 69) or to a control group (n = 70) with "placebo clothing", i.e. clothing that mimicked old age but did not actually impair faculties. Two instruments-Kogan Attitudes Towards Old People Scale (KAOP) and a 1-item scale on Willingness To Care for Older People Scale (WCOP)-were used for data collection at baseline and at completion of SSSP. A Chinese version of Palmore's Facts Aging Quiz (C-FAQ) was used to assess nursing students' knowledge about adult care, and a questionnaire was developed to collect demographic information at baseline. RESULTS: No significant difference between the two groups was found. A significant increase of positive attitudes and of willingness to serve older adults was found in both the control group and the group wearing SSSP. CONCLUSION: Both the SSSP and control intervention could improve the attitudes of nursing students towards older adult care. This study suggests that wearing whatever the nursing students associate with being old, will improve their attitude towards older adult care.

Short-term evaluation of hepatic toxicity of titanium dioxide nanofiber (TDNF).

Various in vitro and in vivo studies have shown titanium dioxide nanoparticles (TDNPs) increase the production of reactive oxygen species and change the expression of genes and proteins involved in the inflammatory response and cell division. Although, the cytotoxicity of TDNPs has been shown to be largely dependent on the characteristics of the particles including shape and surface area. This present study investigates the effects of titanium dioxide nanofibers (TDNFs) with a diameter of 300-800 nm, on the histopathology of liver tissue, changes in feed efficiency and liver weights, changes in hepatic gene expression, and serum biochemical parameters in male Sprague-Dawley rats. Male Sprague-Dawley rats were fed concentrations of 0 ppm, 40 ppm, and 60 ppm TDNF by oral gavage for two weeks. Selected inflammatory response, oxidative stress, and regulatory cell cycle genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Differences in gene expression compared to the 0 ppm group were observed in genes Gnat3, IghA, IL-1ß, p21, p53, and TNF-α. Histopathology, body and liver weights, and feed efficiency showed no significant differences. Albumin levels in all groups were not significantly higher than the reference range while ALT levels for all groups were high compared to the reference value. Currently, the results suggest TDNF does not exhibit significant hepatic toxicity. This may be explained by the rutile crystalline structure of the nanofibers, the lower concentration or the short duration of exposure toxic used during experimentation.

Management of traumatic patellar dislocation in a regional hospital in Hong Kong.

INTRODUCTION: The role of surgery for acute patellar dislocation without osteochondral fracture is controversial. The aim of this study was to report the short-term results of management of patellar dislocation in our institute. METHODS: Patients who were seen in our institution with patella dislocation from January 2011 to April 2014 were managed according to a standardised management algorithm. Pretreatment and 1-year post-treatment International Knee Documentation Committee score, Tegner activity level scale score, and presence of apprehension sign were analysed. RESULTS: A total of 41 patients were studied of whom 20 were first-time dislocators and 21 were recurrent dislocators. Among the first-time dislocators, there was a significant difference between patients who received conservative treatment versus surgical management. The conservative treatment group had a 33% recurrent dislocation rate, whereas there were no recurrent dislocations in the surgery group. There was no difference in Tegner activity level scale score or apprehension sign before and 1 year after treatment, however. Among the recurrent dislocators, there was a significant difference between those who received conservative treatment and those who underwent surgery. The recurrent dislocation rate was 71% in the conservative treatment group versus 0% in the surgery group. There was also significant improvement in International Knee Documentation Committee score from 67.7 to 80.0 (P=0.02), and of apprehension sign from 62% to 0% (P<0.01). CONCLUSIONS: A management algorithm for patellar dislocation is described. Surgery is preferable to conservative treatment in patients who have recurrent patellar dislocation, and may also be preferable for those who have an acute dislocation.

Influence of Perceptual Saliency Hierarchy on Learning of Language Structures: An Artificial Language Learning Experiment.

Psychological experiments have revealed that in normal visual perception of humans, color cues are more salient than shape cues, which are more salient than textural patterns. We carried out an artificial language learning experiment to study whether such perceptual saliency hierarchy (color > shape > texture) influences the learning of orders regulating adjectives of involved visual features in a manner either congruent (expressing a salient feature in a salient part of the form) or incongruent (expressing a salient feature in a less salient part of the form) with that hierarchy. Results showed that within a few rounds of learning participants could learn the compositional segments encoding the visual features and the order between them, generalize the learned knowledge to unseen instances with the same or different orders, and show learning biases for orders that are congruent with the perceptual saliency hierarchy. Although the learning performances for both the biased and unbiased orders became similar given more learning trials, our study confirms that this type of individual perceptual constraint could contribute to the structural configuration of language, and points out that such constraint, as well as other factors, could collectively affect the structural diversity in languages.

Association of endothelin-1 and matrix metallopeptidase-9 with metabolic syndrome in middle-aged and older adults.

BACKGROUND: Metabolic syndrome (MetS) contains a cluster of cardiovascular risk factors. People with MetS are more susceptible to cardiovascular disease, diabetes mellitus, and cancer. Endothelin-1 (ET-1) and matrix metallopeptidase-9 (MMP-9) have been implicated in the development of cardiovascular diseases, diabetes mellitus and cancers. This cross-sectional study aimed to examine the association of ET-1 and MMP-9 with MetS in middle-aged and older Hong Kong Chinese adults. METHODS: 149 adults aged 50 to 92 (n = 75 for non-MetS group and n = 74 for MetS group) were examined. All subjects were screened for MetS according to the diagnostic guideline of the United States National Cholesterol Education Program (NCEP) Expert Panel Adult Treatment Panel (ATP) III criteria. Serum levels of ET-1 and MMP-9 were measured. Independent t test was used to detect differences between non-MetS and MetS groups and between subjects with or without certain metabolic abnormality. The association of the serum concentration of MMP-9 and ET-1 with MetS parameters were examined by Pearson's correlation analysis. RESULTS: Serum level of ET-1 is higher in MetS-positive subjects and in subjects with high blood pressure, elevated fasting blood glucose, and central obesity. The serum concentration of MMP-9 is higher in subjects positively diagnosed with MetS and subjects with high blood pressure, elevated fasting blood glucose, low blood high-density lipoprotein-cholesterol (HDL-C), high blood triglycerides, and central obesity. Correlation analyses revealed that serum concentration of ET-1 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. MMP-9 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. CONCLUSION: Serum ET-1 is higher in subjects with hypertension, hyperglycemia, central obesity or MetS. Serum MMP-9 is higher in subjects diagnosed with MetS or having either one of the MetS parameters. Both circulating levels of ET-1 and MMP-9 are correlated to systolic blood pressure, waist circumference, fasting blood glucose, HDL-C, and age. Further research is needed to fully dissect the role of ET-1 and MMP-9 in the development of cancers, diabetes and cardiovascular disease in relation to MetS.

Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma.

Zinc-finger, MYND-type containing 10 (ZMYND10), or more commonly called BLU, expression is frequently downregulated in nasopharyngeal carcinoma (NPC) and many other tumors due to promoter hypermethylation. Functional evidence shows that the BLU gene inhibits tumor growth in animal assays, but the detailed molecular mechanism responsible for this is still not well understood. In current studies, we find that 93.5% of early-stage primary NPC tumors show downregulated BLU expression. Using a PCR array, overexpression of the BLU gene was correlated to the angiogenesis network in NPC cells. Moreover, expression changes of the MMP family, VEGF and TSP1, were often detected in different stages of NPC, suggesting the possibility that BLU may be directly involved in the microenvironment and anti-angiogenic activity in NPC development. Compared with vector-alone control cells, BLU stable transfectants, derived from poorly-differentiated NPC HONE1 cells, suppress VEGF165, VEGF189 and TSP1 expression at both the RNA and protein levels, and significantly reduce the secreted VEGF protein in these cells, reflecting an unknown regulatory mechanism mediated by the BLU gene in NPC. Cells expressing BLU inhibited cellular invasion, migration and tube formation. These in vitro results were further confirmed by in vivo tumor suppression and a matrigel plug angiogenesis assay in nude mice. Tube-forming ability was clearly inhibited, when the BLU gene is expressed in these cells. Up to 70-90% of injected tumor cells expressing increased exogenous BLU underwent cell death in animal assays. Overexpressed BLU only inhibited VEGF165 expression in differentiated squamous NPC HK1 cells, but also showed an anti-angiogenic effect in the animal assay, revealing a complicated mechanism regulating angiogenesis and the microenvironment in different NPC cell lines. Results of these studies indicate that alteration of BLU gene expression influences anti-angiogenesis pathways and is important for the development of NPC.

Strontium exerts dual effects on calcium phosphate cement: Accelerating the degradation and enhancing the osteoconductivity both in vitro and in vivo.

Calcium phosphate cements (CPCs) have long been used as osteoconductive bone substitutes in the treatment of bone defects. However, the degradation rate of CPC is typically too slow to match the new bone growth rate. It is known that strontium increases the solubility of hydroxyapatite as well as exerts both anabolic and anticatabolic effects on bone. Therefore, we hypothesized that the incorporation of strontium would accelerate the degradation rate and enhance the osteoconductivity of CPC. In this study, Three groups, CPC (0% Sr-CPC), 5% Sr-CPC, and 10% Sr-CPC, were prepared, with the total molar ratio for Sr/(Sr+Ca) in the cement powder phase being 0, 5, and 10%, respectively. In the immersion test, less residual weight was observed in both 5% Sr-CPC and 10% Sr-CPC groups than CPC group. In addition, a higher osteoblastic cell proliferation rate and alkaline phosphatase activity were obtained in the strontium groups. In a rat femur bone defect model comparing CPC with 10% Sr-CPC, at 2 weeks postoperation, early endochondral ossification was found in the 10% Sr-CPC group, whereas only fibrous tissue was observed in control group; at 4-16 weeks postoperation, progressive osteoconduction toward the cement was observed in both groups. At 32 weeks, a higher peri-cement bone area and reduced cement area were noted in the 10% Sr-CPC group. In conclusion, in the 10% Sr-CPC group, strontium exerts dual effects on CPC: accelerating degradation rate and enhancing osteoconductivity, as shown here both in vitro and in vivo.