Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.

OBJECTIVES: To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses. METHODS: OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium. RESULTS: We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an "arthritis" specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively. CONCLUSION: This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.

GAD65 as a potential marker for cognitive performance in an adult population with prediabetes.

BACKGROUND: Diabetes mellitus (DM) is a well-known risk factor for cognitive dysfunction in aged populations. However, there are inconsistent reports about impaired fasting glucose or prediabetes as an independent risk factor for cognitive function. Glutamic acid decarboxylase 65 (GAD65) is the key enzyme responsible for γ-aminobutyric acid synthesis in the central nervous system. Antibodies against GAD65 (GAD65Abs) are not only detected in approximately 80% of early-onset type 1 DM, but also linked to several neurological disorders. AIM: This study aims to investigate the association between GAD65Ab titer levels and cognitive performance. In addition, we assessed the effect of GAD65Ab on cognitive function in adults with normal fasting glucose, prediabetes and DM. METHODS: A total of 328 subjects aged 49.10 ± 5.72 years were enrolled from the Third Health and Nutrition Examination Survey dataset. Cognitive performance was assessed by three computerized neurobehavioral tests, including the serial digit learning test, simple reaction time test (SRTT) and symbol-digit substitution test (SDST). RESULTS: Subjects with higher GAD65Ab titers had significantly poorer cognitive function in the SRTT and SDST (P < 0.05). Additionally, GAD65Ab was associated with cognitive decline in non-diabetic adults after adjusting for a number of relevant variables (P < 0.05 in both SRTT and SDST). CONCLUSIONS: These results indicate that GAD65Ab may be a potential marker for cognitive impairment in non-diabetic adults.

The association between septicemia and the risk of multiple sclerosis: a nationwide register-based retrospective cohort study in Taiwan.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Few studies focused on the relationship between septicemia and MS. AIM: To evaluate the potential impact of septicemia on risk for MS. DESIGN: Two cohorts of patients with septicemia and without septicemia were followed up for the occurrence of MS. METHODS: Patients of 482 790 with septicemia was enrolled from the National Health Insurance Research Database between 2001 and 2011 as the study group to match the 1 892 820 individuals, as the control group, by age and gender. Incidence of MS in both groups was calculated. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR) for MS between groups. RESULTS: Septicemia patients had a 3.06-fold (95% CI: 2.16-4.32, P < 0.001) greater risk of developing MS than the matched group. In addition, higher severity of septicemia was associated with higher risk of developing MS (moderate: HR = 4.03, 95% CI: 2.53-6.45, P < 0.001; severe: HR = 11.1, 95% CI: 7.01-17.7, P < 0.001). Similar results also occurred in both male and female patients with septicemia (male: HR = 4.06, 95% CI: 2.17-7.58, P < 0.001; female: HR = 2.72, 95% CI: 1.79-4.11, P < 0.001). Patients without counterpart comorbidities had a significantly higher risk of MS than the controlled group (HR = 3.02, 95% CI: 2.10-4.35, P < 0.001). CONCLUSION: The results indicated septicemia is linked to an increased risk for MS. Aggressively preventing and treating septicemia may be warranted for one of precautionary strategies of MS.

Quantum thermodynamics from the nonequilibrium dynamics of open systems: Energy, heat capacity, and the third law.

In a series of papers, we intend to take the perspective of open quantum systems and examine from their nonequilibrium dynamics the conditions when the physical quantities, their relations, and the laws of thermodynamics become well defined and viable for quantum many-body systems. We first describe how an open-system nonequilibrium dynamics (ONEq) approach is different from the closed combined system +  environment in a global thermal state (CGTs) setup. Only after the open system equilibrates will it be amenable to conventional thermodynamics descriptions, thus quantum thermodynamics (QTD) comes at the end rather than assumed in the beginning. The linkage between the two comes from the reduced density matrix of ONEq in that stage having the same form as that of the system in the CGTs. We see the open-system approach having the advantage of dealing with nonequilibrium processes as many experiments in the near future will call for. Because it spells out the conditions of QTD's existence, it can also aid us in addressing the basic issues in quantum thermodynamics from first principles in a systematic way. We then study one broad class of open quantum systems where the full nonequilibrium dynamics can be solved exactly, that of the quantum Brownian motion of N strongly coupled harmonic oscillators, interacting strongly with a scalar-field environment. In this paper, we focus on the internal energy, heat capacity, and the third law. We show for this class of physical models, amongst other findings, the extensive property of the internal energy, the positivity of the heat capacity, and the validity of the third law from the perspective of the behavior of the heat capacity toward zero temperature. These conclusions obtained from exact solutions and quantitative analysis clearly disprove claims of negative specific heat in such systems and dispel allegations that in such systems the validity of the third law of thermodynamics relies on quantum entanglement. They are conceptually and factually unrelated issues. Entropy and entanglement will be the main theme of our second paper on this subject matter.

TSG-6 - a double-edged sword for osteoarthritis (OA).

PURPOSE: To explore mechanisms underlying the association of TSG-6 with osteoarthritis (OA) progression. METHODS: TSG-6-mediated heavy chain (HC) transfer (TSG-6 activity) and its association with inflammatory mediators were quantified in knee OA (n=25) synovial fluids (SFs). Paired intact and damaged cartilages from the same individuals (20 tibial and 12 meniscal) were analyzed by qRT-PCR and immunohistochemistry (IHC) for gene and protein expression of TSG-6 and components of Inter-alpha-Inhibitor (IαI) and TSG-6 activity ± spiked in IαI. Primary chondrocyte cultures (n=5) ± IL1ß or TNFα were evaluated for gene expression. The effects of TSG-6 activity on cartilage extracellular matrix (ECM) assembly were explored using quantitative hyaluronan (HA)-aggrecan binding assays. RESULTS: TSG-6 activity was significantly associated (R > 0.683, P < 0.0002) with inflammatory mediators including TIMP-1, A2M, MMP3, VEGF, VCAM-1, ICAM-1 and IL-6. Although TSG-6 protein and mRNA were highly expressed in damaged articular and meniscal cartilage and cytokine-treated chondrocytes, there was little or no cartilage expression of components of the IαI complex (containing HC1). By IHC, TSG-6 was present throughout lesioned cartilage but HC1 only at lesioned surfaces. TSG-6 impaired HA-aggrecan assembly, but TSG-6 mediated HA-HC formation reduced this negative effect. CONCLUSIONS: TSG-6 activity is a global inflammatory biomarker in knee OA SF. IαI, supplied from outside cartilage, only penetrates the cartilage surface, restricting TSG-6 activity (HC transfer) to this region. Therefore, unopposed TSG-6 in intermediate and deep regions of OA cartilage could possibly block matrix assembly, leading to futile synthesis and account for increased risk of OA progression.

The potential impact of sleep-related movement disorders on stroke risk: a population-based longitudinal study.

BACKGROUND: Sleep-related movement disorders (SRMD) have been shown to increase the risk of cardiovascular diseases. However, the relationship between SRMD and stroke remains unclear. AIM: To explore the relationship between SRMD and stroke in the general population. DESIGN: Two cohorts of patients with SRMD and without SRMD were followed up for the occurrence of hemorrhagic and ischemic stroke. METHODS: The study cohort enrolled 604 patients who were initially diagnosed as SRMD between 2000 and 2005. 2,416 age- and sex-matched patients without prior stroke were selected as the comparison cohort. A Cox-proportional hazard regression analysis was performed for multivariate adjustment. RESULTS: Patients with SRMD had a higher risk for developing all-cause stroke [adjusted hazard ratio (HR) = 2.29, 95% confidence interval (CI) = 1.42-3.80]. Patients of below 45 years old had the greatest stroke risk (HR = 4.03, 95% CI = 3.11-5.62), followed by patients aged ≥65 years (HR = 2.64, 95% CI = 1.12-3.44) and 45-64 years (HR = 1.07, 95% CI = 1.02-1.71). The age-stratified analysis suggested that the increased risk of hemorrhagic stroke was more significant than ischemic stroke among all age groups. Furthermore, males with SRMD were at greater risk to develop all-cause stroke (HR = 2.98, 95% CI = 1.74-4.50) than that of females (HR = 1.94, 95% CI = 1.01-3.77). CONCLUSIONS: Patients with SRMD were found to have an increased risk of all-cause stroke along with a higher possibility of hemorrhagic stroke over ischemic stroke.

Detection of the Severe Acute Respiratory Syndrome-Related Coronavirus and Alphacoronavirus in the Bat Population of Taiwan.

Bats have been demonstrated to be natural reservoirs of severe acute respiratory syndrome coronavirus (SARS CoV) and Middle East respiratory syndrome (MERS) CoV. Faecal samples from 248 individuals of 20 bat species were tested for partial RNA-dependent RNA polymerase gene of CoV and 57 faecal samples from eight bat species were tested positive. The highest detection rate of 44% for Scotophilus kuhlii, followed by 30% for Rhinolophus monoceros. Significantly higher detection rates of coronaviral RNA were found in female bats and Scotophilus kuhlii roosting in palm trees. Phylogenetic analysis classified the positive samples into SARS-related (SARSr) CoV, Scotophilus bat CoV 512 close to those from China and Philippines, and Miniopterus bat CoV 1A-related lineages. Coronaviral RNA was also detected in bat guano from Scotophilus kuhlii and Myotis formosus flavus on the ground and had potential risk for human exposure. Diverse bat CoV with zoonotic potential could be introduced by migratory bats and maintained in the endemic bat population in Taiwan.

Noninvasive tongue-motion controlled computer mouse for the disabled.

BACKGROUND: A patient whose spinal cord was damaged due to accident may result in Tetraplegia or lose the ability to control his/her daily living environment. Currently, patients must use an invasive tool tongue movement, to help the patient communicate with the external environment. OBJECTIVE: This study designed a non-invasive tongue movement computer mouse system that allows the patient to use tongue movement to control a computer to communicate with the external environment. METHODS: Via a pressure sensor and assistive holder designed in this study, the pressure sensor can be moved using the assistive holder close to the mylohyoid muscle of the patient's lower jaw. The changes in pressure from the mylohyoid muscle are converted into computer mouse control signals to control a computer to communicate with the external environment. RESULTS: This study is based on ISO9241-Part 9 to design four kinds of training modes with varying difficulties. The data were collected from five able persons participating in the test over 7 days. The data includes throughput, path efficiency, test completion time and reaction time. The data verifies that the proposed system is stable and practical for persons with disabilities. CONCLUSION: The non-invasive computer mouse system for sensing tongue movement can completely breakthrough the limitations of the invasive tongue movement sensing system. This study uses non-invasive, simple tongue movements that correspond to the stretching and shrinking of the lower jaw mylohyoid muscle to control the computer mouse.

Biocompatibility of a fish scale-derived artificial cornea: Cytotoxicity, cellular adhesion and phenotype, and in vivo immunogenicity.

PURPOSE: To determine whether a fish scale-derived collagen matrix (FSCM) meets the basic criteria to serve as an artificial cornea, as determined with in vitro and in vivo tests. METHODS: Primary corneal epithelial and stromal cells were obtained from human donor corneas and used to examine the (in)direct cytotoxicity effects of the scaffold. Cytotoxicity was assessed by an MTT assay, while cellular proliferation, corneal cell phenotype and adhesion markers were assessed using an EdU-assay and immunofluorescence. For in vivo-testing, FSCMs were implanted subcutaneously in rats. Ologen(®) Collagen Matrices were used as controls. A second implant was implanted as an immunological challenge. The FSCM was implanted in a corneal pocket of seven New Zealand White rabbits, and compared to sham surgery. RESULTS: The FSCM was used as a scaffold to grow corneal epithelial and stromal cells, and displayed no cytotoxicity to these cells. Corneal epithelial cells displayed their normal phenotypical markers (CK3/12 and E-cadherin), as well as cell-matrix adhesion molecules: integrin-α6 and ß4, laminin 332, and hemi-desmosomes. Corneal stromal cells similarly expressed adhesion molecules (integrin-α6 and ß1). A subcutaneous implant of the FSCM in rats did not induce inflammation or sensitization; the response was comparable to the response against the Ologen(®) Collagen Matrix. Implantation of the FSCM in a corneal stromal pocket in rabbits led to a transparent cornea, healthy epithelium, and, on histology, hardly any infiltrating immune cells. CONCLUSION: The FSCM allows excellent cell growth, is not immunogenic and is well-tolerated in the cornea, and thus meets the basic criteria to serve as a scaffold to reconstitute the cornea.

5α-Reductase inhibitors increase acute coronary syndrome risk in patients with benign prostate hyperplasia.

BACKGROUND: This study explored the possible association between the use of two typical 5ARIs (finasteride and dutasteride) and the risk of acute coronary syndrome (ACS) in patients with benign prostate hyperplasia (BPH). METHODS: From the claims data of the Taiwan National Health Insurance (NHI) Taiwan, we identified 1843 ACS cases among BPH patients and randomly selected 7330 controls without ACS, with a similar mean age of 73 years. Multivariate logistic regression analysis estimated the odds ratio (OR) and 95 % confidence interval (CI) for the relationship between the 5ARIs medications and ACS risk. RESULTS: We found that BPH patients who had received treatment with both finasteride and dutasteride were at a higher risk of ACS with an OR of 3.47 (95 % CI 1.05-11.5), compared to patients without 5ARIs treatment. Furthermore, the dosage analysis showed that there were no significant associations between ACS risk and uses of a single drug medication regardless the dosages. The ORs for those who took only dutasteride were 1.07 (95 % CI 0.39-2.99) with low dose and 0.73 (95 % CI 0.38-1.44) with high dose. The ORs for those who took only finasteride were 1.30 (95 % CI 0.89-1.92) with low dose and 0.98 (95 % CI 0.19-5.13) with high dose. CONCLUSION: This population-based nested case-control study suggests that 5ARI use may increase ACS risk among patients with BPH when patients were exposed to both finasteride and dutasteride.

Insights into osteoarthritis progression revealed by analyses of both knee tibiofemoral compartments.

OBJECTIVE: To identify disease relevant genes and pathways associated with knee Osteoarthritis (OA) progression in human subjects using medial and lateral compartment dominant OA knee tissue. DESIGN: Gene expression of knee cartilage was comprehensively assessed for three regions of interest from human medial dominant OA (n = 10) and non-OA (n = 6) specimens. Histology and gene expression were compared for the regions with minimal degeneration, moderate degeneration and significant degeneration. Agilent whole-genome microarray was performed and data were analyzed using Agilent GeneSpring GX11.5. Significant differentially regulated genes were further investigated by Ingenuity Pathway Analysis (IPA) to identify functional categories. To confirm their association with disease severity as opposed to site within the knee, 30 differentially expressed genes, identified by microarray, were analyzed by quantitative reverse-transcription polymerase chain reaction on additional medial (n = 16) and lateral (n = 10) compartment dominant knee OA samples. RESULTS: A total of 767 genes were differentially expressed ≥ two-fold (P ≤ 0.05) in lesion compared to relatively intact regions. Analysis of these data by IPA predicted biological functions related to an imbalance of anabolism and catabolism of cartilage matrix components. Up-regulated expression of IL11, POSTN, TNFAIP6, and down-regulated expression of CHRDL2, MATN4, SPOCK3, VIT, PDE3B were significantly associated with OA progression and validated in both medial and lateral compartment dominant OA samples. CONCLUSIONS: Our study provides a strategy for identifying targets whose modification may have the potential to ameliorate pathological alternations and progression of disease in cartilage and to serve as biomarkers for identifying individuals susceptible to progression.

[Decellularized collagen matrix from tilapia fish scales for corneal reconstruction (BioCornea)]. / Dezellularisierte Kollagenmatrix aus der Schuppe des Tilapia-Fisches als Hornhautersatz ("BioCornea").

BACKGROUND: The worldwide need for donor corneal tissue clearly exceeds the availability of transplantable human tissue; therefore, recent efforts aim to identify and characterize alternative tissues, such as decellularized collagen scaffolds. OBJECTIVES: The transparent fish scales of tilapia (Oreochromis mossambicus) were analyzed as a potential alternative for corneal reconstruction ("BioCornea"). MATERIAL AND METHODS: The article gives a review of the literature and own preliminary results. After decellularization the tissue characteristics of the fish scales, the repopulation with corneal epithelium and stromal cells, immunogenicity, the feasibility of corneal transplantation and the angiogenic properties were analyzed in vitro and in various animal models. RESULTS: The fish scales mainly consist of collagen type I and show an architecture that is similar to the human cornea. Corneal epithelium and stromal cells are able to grow over and into the scaffold. It is possible to transplant fish scales in various animal models without severe inflammatory responses. Furthermore, in mice, less blood and lymphatic vessels grow into the xenograft when compared to conventional allogenic transplants. CONCLUSION: Preliminary results with decellularized tilapia fish scales as an alternative for corneal reconstruction ("BioCornea") are promising.

Increased level of MSU crystal-bound protein apolipoprotein A-I in acute gouty arthritis.

BACKGROUND: Gout is a common form of inflammatory arthritis that is triggered by the crystallization of monosodium urate (MSU). We investigated the potential proteins that relate to the pathogenesis or the spontaneous resolution of acute gouty arthritis. METHOD: We screened for differentially expressed proteins in the plasma of patients with acute gouty arthritis using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) identification. We confirmed these findings in a population study of 209 subjects, and further determined the protein profile of the synovial fluid (SF) from 24 gouty patients during acute attack by liquid chromatography coupled with tandem MS (LC/MS/MS). RESULTS: The highly expressed apolipoprotein A-I (apoA-I) was identified in the plasma of acute gouty patients compared with healthy controls. Moreover, we detected high levels of SF apoA-I in 83.3% of acute gouty patients during attack. From the population study, apoA-I was increasingly associated with normouricaemia, hyperuricaemia, and acute gouty arthritis (ptrend < 0.001), and plasma uric acid (UA) and apoA-I were positively correlated (p = 0.0156). We used a human liver cell model and found that UA enhanced the hepatic apoA-I mRNA expression level (ptrend < 0.01) and apoA-I secretion level (ptrend = 0.002) in a dose-dependent manner. An elevated MSU concentration caused the endogenous apoA-I to deplete gradually. CONCLUSIONS: Based on the role of apoA-I in anti-inflammation, our observational data in acute gout support the hypothesis that apoA-I expression can be induced under the condition of a high concentration of UA and its elevated level may be implicated in the spontaneous resolution of acute gouty arthritis.

FES for abnormal movement of upper limb during walking in post-stroke subjects.

BACKGROUND: Hemiplegia can cause accidental falls, as the patients place their arms in front of their chests or next to the hips when they walk. This is due to limitations in the ability to swing their arms during walking. OBJECTIVE: This study proposes a functional electrical stimulator approach in order to improve the foot drop and abnormal movement of the upper limbs during walking. The goal of this study is to verify the feasibility of improving the foot drop and arm swing problems of hemiplegic patients using electrical stimulators in a clinical trial. METHODS: The present study utilizes a functional electrical stimulator found on the market. The stimulator is controlling the gait and arm swing of the patient while the patient is walking. It can help him or her restore regular gait cycles and arm swings. The FES device can also train the patient to walk safely and regain control of his or her arm swing. After the four-week training, the subjects had to walk 10 meters without the FES system. The step length, step time, and joint goniograms were recorded in order to determine whether there was any improvement. RESULTS: After the four-week training was concluded, the three post-stroke patients showed an improvement in arm swing angle when walking. The improvement was found to be 7.16% in the first patient, 43.06% in the second, and 54.66% in the third. These results are all statistically significant. The t-test had a p-value 0.012 (p< 0.05), which demonstrated that the method used in the present study had the potential to significantly improve the arm swing of post-stroke patients. CONCLUSIONS: The present study showed that a traditional foot drop functional electrical stimulator providing stimulation also to the patient's upper limbs, while being triggered by a foot switch under his or her heel, can help the patient to swing the arms and reduce the foot drop. The method has significant effect on traditional foot drop therapy. The subjects' high degree of acceptance and willingness to commit to long-term use showed that the method is indeed worthy of further research.

Ultrasound-assisted extraction of phenolic compounds from Phyllanthus emblica L. and evaluation of antioxidant activities.

OBJECTIVE: The objective of this study was to optimize ultrasound-assisted extraction of phenolic compounds from Phyllanthus emblica. METHODS: Extracts obtained by UAE were evaluated for their antioxidant activities. Extraction experiments were carried out with three factors and three levels namely extraction time (varying from 15 to 60 min), ethanol concentration (varying from 50 to 90%) and frequency (varying from 28 to 56 kHz). RESULTS: The results showed that the UAE optimal conditions of extracting total phenol components were as follows: 15 min of extraction time, 60°C of extraction temperature, 70% of ethanol concentration, 56 kHz of ultrasonic frequency and a 1: 50 solid to solvent ratio. Under optimal conditions, the leaching-out rate of phenolic compounds was up to 55.34 mg g(-1) , and the yield of crude extract of P. emblica was up to 56.82%. The results reveal that the yield of phenolic compounds of UAE (56.82%) is higher than that of conventional solvent extraction (16.78%). Furthermore, the antioxidant activities of ethanol extracts obtained by UAE were evaluated in terms of activities of DPPH (1,1'-diphenyl-2-2'-picrylhydrazyl) radical scavenging activity, total antioxidant activity, metal chelating activity, and reducing power. P. emblica extracts obtained by UAE showed high antioxidant activity (26.00, 50.11 and 115.91 µg mL(-1) of IC50 values for DPPH radicals, total antioxidant ability and chelating ability of ferrous ion). CONCLUSION: The result of this study showed that UAE was a suitable method for the extraction of total phenolic compounds. Moreover, the author's main finding in this work is the fact that phenolic compounds from P. emblica show excellent antioxidant activity in multi-test systems.

Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization.

OBJECTIVES: Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases. METHODS: In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1. RESULTS: Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies. CONCLUSION: Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome.

Central sleep apnea in obese children with sleep-disordered breathing.

OBJECTIVES: In contrast to obstructive sleep apnea (OSA), central sleep apnea (CSA) in obese children has received lesser attention. As pediatric CSA is more prevalent than expected and adversely impacts health, this study aims to elucidate the major factors associated with central apnea index (CAI) and compare CSA between obese and non-obese children. METHODS: Retrospective analysis was performed in a tertiary referral medical center. Children with sleep-disordered breathing (SDB) ranging from 2-18 years old were enrolled. All participants completed history taking, otolaryngological examination and overnight polysomnography. CSA was defined as having CAI exceeding 1 h(-1). CAI and the prevalence of CSA were analyzed in children of different age groups, weight statuses and adenotonsillar sizes. RESULTS: A total of 487 cases were included. The prevalence of CSA was 13.3% (65/487). CAI was negatively correlated with age (r=-0.32, P<0.001). Obese children had a significantly lower CAI than that of non-obese ones (0.20 ± 0.36 vs 0.48 ± 0.82 h(-1), P<0.001). Multiple linear regression analysis demonstrated a relationship between CAI, age and obesity as 'CAI=0.883-0.055 × Age -0.22 × (Obesity)'. CONCLUSIONS: In children with SDB, younger ones have a significantly higher CAI than older ones. Additionally, obese children had a lower CAI than non-obese ones.

A nationwide population-based retrospective cohort study: increased risk of acute coronary syndrome in patients with ankylosing spondylitis.

OBJECTIVES: To compare the risk of acute coronary syndrome (ACS) between patients with and without ankylosing spondylitis (AS). METHOD: This retrospective cohort study identified all patients with AS aged ≥ 18 years newly diagnosed from 2000 to 2009, registered in the National Health Insurance Research Database (NHIRD) in Taiwan. The non-AS cohort consisted of fourfold randomly selected control patients free of AS, frequency matched by age, sex, and diagnosis year. The incidence of ACS was determined for both AS and non-AS cohorts. RESULTS: We selected 6262 patients with AS and 25 048 patients without AS. The patients with AS were more prevalent than those without, with co-morbidities of hypertension, diabetes mellitus (DM), hyperlipidaemia, stroke, and peripheral vascular diseases. The overall incidence rate of ACS was higher in the AS cohort than in the non-AS cohort (4.4 vs. 2.9 per 1000 person-years), with an adjusted hazard ratio (aHR) of 1.36 [95% confidence interval (CI) 1.16-1.59]. AS patients with co-morbidities of hypertension, DM, and cancer had an aHR of 7.74 for ACS, compared to those without these co-morbidities. CONCLUSIONS: AS patients are at higher risk of ACS compared with non-AS subjects. Management of CV risk factors should be taken into account for the treatment of patients with AS, especially for patients with co-morbidities of hypertension, DM, and cancer.

Direct assessment of articular cartilage and underlying subchondral bone reveals a progressive gene expression change in human osteoarthritic knees.

OBJECTIVE: To evaluate the interaction of articular cartilage (AC) and subchondral bone (SB) through analysis of osteoarthritis (OA)-related genes of site-matched tissue. DESIGN: We developed a novel method for isolating site-matched overlying AC and underlying SB from three and four regions of interest respectively from the human knee tibial plateau (n = 50). For each site, the severity of cartilage changes of OA were assessed histologically, and the severity of bone abnormalities were assessed by microcomputed tomography. An RNA isolation procedure was optimized that yielded high quality RNA from site-matched AC and SB tibial regions. Quantitative polymerase chain reaction (Q-PCR) analysis was performed to evaluate gene expression of 61 OA-associated genes for correlation with cartilage integrity and bone structure parameters. RESULTS: A total of 27 (44%) genes were coordinately up- or down-regulated in both tissues. The expression levels of 19 genes were statistically significantly correlated with the severity of AC degeneration and changes of SB structure; these included: ADAMTS1, ASPN, BMP6, BMPER, CCL2, CCL8, COL5A1, COL6A3, COL7A1, COL16A1, FRZB, GDF10, MMP3, OGN, OMD, POSTN, PTGES, TNFSF11 and WNT1. CONCLUSIONS: These results provide a strategy for identifying targets whose modification may have the potential to ameliorate pathological alterations and progression of disease in both AC and SB simultaneously. In addition, this is the first study, to our knowledge, to overcome the major difficulties related to isolation of high quality RNA from site-matched joint tissues. We expect this method to facilitate advances in our understanding of the coordinated molecular responses of the whole joint organ.