Graphene-All-Around Cobalt Interconnect with a Back-End-of-Line Compatible Process.

The graphene-all-around (GAA) structure has been verified to grow directly at 380 °C using hot-wire chemical vapor deposition, within the thermal budget of the back end of the line (BEOL). The cobalt (Co) interconnects with the GAA structure have demonstrated a 10.8% increase in current density, a 27% reduction in resistance, and a 36 times longer electromigration lifetime. X-ray photoelectron spectroscopy and density functional theory calculations have revealed the presence of bonding between carbon and Co, which makes the Co atom more stable to resist external forces. The ability of graphene to act as a diffusion barrier in the GAA structure was confirmed through time-dependent dielectric breakdown measurement. The Co interconnect within the GAA structure exhibits enhanced electrical properties and reliability, which indicates compatibility applications as next-generation interconnect materials in CMOS BEOL.

IL-1ß stimulated human umbilical cord mesenchymal stem cells ameliorate rheumatoid arthritis via inducing apoptosis of fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is characterized by synovial proliferation and lymphocyte accumulation leading to progressive damage of the periarticular bone and the articular cartilage. The hyperplasia of the synovial intima lining mainly consists of fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) which exhibit apoptosis-resistance, hyper-proliferation, and high invasiveness. The therapeutic efficacy of mesenchymal stem cells (MSCs) treatment in RA has been shown to be due to its immuno-regulatory ability. However, the exact factors and mechanisms involved in MSCs treatment in RA remain unclear. In this study, TRAIL receptor-Death receptor 4 (DR4), DR5, and LFA-1 ligand-intercellular adhesion molecule-1 (ICAM-1) were upregulated in IL-1ß-stimulated HFLS-RA. We demonstrated that the total cell number of IL-1ß-stimulated hUCMSCs adhering to IL-1ß-stimulated HFLA-RA increased via LFA-1/ICAM-1 interaction. Direct co-culture of IL-1ß-stimulated hUCMSCs with IL-1ß-stimulated HFLS-RA increased the apoptosis of HFLS-RA. RA symptoms in the CIA mouse model improved after administration of IL-1ß-stimulated hUCMSCs. In conclusion, IL-1ß-stimulated hUCMSCs adhering to HFLS-RA occurred via LFA-1/ICAM-1 interaction, apoptosis of HFLS-RA was induced via TRAIL/DR4, DR5 contact, and RA symptoms and inflammation were significantly improved in a CIA mouse model. The results of this study suggest that IL-1ß-stimulated hUCMSCs have therapeutic potential in RA treatment.

Anti-tumor Effects of IL-1ß Induced TRAIL-Expressing hUCMSCs on Embelin Treated Breast Cancer Cell Lines.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) have high therapeutic value in cancer treatment. We have found that pre-activating hUCMSCs with IL-1ß promotes tumor necrosis factor-related apoptosis inducing ligand (TRAIL) expression and facilitates anti-tumor effect. Furthermore, embelin has been found to induce apoptosis of different cancer cell lines by upregulating the expression of TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5). This study investigated whether IL-1ß induced TRAIL-expressing hUCMSCs, in combination with low-dose embelin, could further induce apoptosis in breast cancer cell lines. MATERIALS AND METHODS: MTT assay was used to examine the cytotoxicity of embelin in MDA-MB-231 and MCF-7. To detect the interested protein expression in cells, Western blot and cell immunofluorescence were used to double-confirm the observed results. Annexin V/PI apoptosis assay was detected by flow cytometry to analyze the apoptosis rate of embelin treated breast cancer cell lines and the effect of co-culturing with breast cancer cells and hUCMSCs. RESULTS: Using Western blot and immunofluorescence, we found that breast cancer cell lines treated with low-dose embelin (2.5-5 µM) increased the expression of apoptosis-related receptor DR4, DR5 and the cleaved caspase 8, 9 and 3. Moreover, TRAIL expression was enhanced in IL-1ß induced hUCMSCs. Combining these observations, we expected that coculturing IL-1ß induced hUCMSCs with low dose embelin treated MDA-MB-231 and MCF-7 cells might enhance the apoptosis of breast cancer cells. We confirmed via flow cytometry that coculture of IL-1ß induced TRAIL-expressing hUCMSCs and embelin treated MDA-MB-231 and MCF-7 cells enhances the apoptosis rate of these breast cancer cells. CONCLUSION: We found that embelin upregulated the expression of DR4 and DR5 to increase the TRAIL-mediated apoptosis in breast cancer cell lines. Low dose embelin treated breast cancer cell lines in combination with IL-1ß induced TRAIL-expressing hUCMSCs may become a potential anti-tumor therapy.

Impacts of HER2 immunohistochemical scores on response and outcomes of HER2-positive breast cancers after neoadjuvant therapy.

BACKGROUND: Neoadjuvant systemic therapy (NST) is conducted in increased number of patients with breast cancer overexpressing human epidermal growth factor receptor 2 (HER2). Whether the intensity of HER2 protein expression determines response to treatment is challenged. This study aims to analyze the impact of HER2 immunohistochemical (IHC) scores on NST response and survival outcome. METHODS: We analyzed a total of 197 patients with HER2-positive breast cancer receiving NST and definite surgery from a prospectively collected database. The analyzed endpoints included pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). More patients with IHC 2+/ in situ hybridization (ISH)-positive tumors presented positive for hormonal receptors, compared with those with IHC 3+ tumors. No clinicopathological features except tumor necrosis were significantly associated with pCR. RESULTS: Both positive hormone receptors and IHC scores stood on the borderline in statistical analysis. IHC 3+ group tends to present a higher pCR rate than IHC 2+/ISH+ groups (52.5% vs. 34.3%). Patients who achieved pCR had better survival outcome than that of non-pCR group. The impact of pCR on survival reached the statistical significance in the IHC 3+ group both in DFS (90.9% vs. 76.5%; p = 0.004) and OS (97.4% vs. 83.2%; p = 0.002). Multivariate analysis demonstrated IHC scores as an independent predictor of survival outcome with the adjustment of tumor staging and pCR. CONCLUSION: HER2 IHC score is an independent predictor for outcome. IHC 3+ tumors presented a trend of higher pCR rate and better outcome in HER2-positive breast cancer patients who receive NST.

Integrated infrared thermography and accelerometer-based behavior logger as a hoof lesion identification tool in dairy cows with various foot diseases under subtropical climates.

Infrared thermography (IRT) can measure a temperature change on the surface of objects, and is widely used as an inflammation or fever detection tool. The objective of this longitudinal study was to investigate the feasibility of detecting hoof lesion cattle using IRT under subtropical climate conditions. The experiment was conducted in two free-stall commercial dairy farms and 502 dairy cows participated between August 2020 and March 2022. Before hoof trimming, the portable IRT was used to measure the maximum temperature of each hoof from three shooting directions, including anterior (hoof coronary band), lateral (hoof lateral coronary band), and posterior (skin between heel and bulbs). In order to evaluate the effect of hoof lesions on the behavior of dairy cows, we also collected behavior data by automated accelerometers. The results indicated that the temperature of hooves with lesions was significantly higher than that of sound hooves in hot environments regardless of the shooting directions (P < 0.0001). In all of three shooting directions, the maximum temperature of feet with severe lesion was significantly higher than those of feet with mild lesion and sound feet (P < 0.05). Cows with lesion feet had lower daily activity and feeding time than sound cows before clinical diagnosis (P < 0.05). Furthermore, we used thresholds of both anterior hoof temperature at 32.05 °C and average daily activity at 410.5 (arbitrary unit/d) as a lame cow detecting tool. The agreement of this integrated tool reached 75% with clinical diagnosis, indicating that this integrated approach may be feasible for practice in dairy farm. In conclusion, IRT has the potential to be used as a hoof lesion detecting tool under subtropical climate conditions when using sound hoof temperature as reference points, and detection precision can be improved when IRT integrated with automated accelerometers as a lame cow detecting tool.

Infrared thermography (IRT) has been considered as one of the most effective tools for identification of hoof lesions in dairy cows. However, ambient temperature had been proven to affect the measurement of the IRT. The purpose of this current study is to investigate whether IRT could detect changes in hoof temperature on the feet with lesions under subtropical climate conditions. The results indicated that the maximum temperature of affected hoof was significantly higher than that of nonaffected hoof even in hot environments. The diagnostic accuracy of the IRT could be above 70%. When combining daily activity value collected by accelerometer of each cow with hoof temperature as a hoof lesion detected criterion, the accuracy of this integrated diagnostic tool could elevate to 75%. This suggests that IRT can be used as a hoof lesion detecting tool under subtropical climate conditions.

Verification of the critical-care pain observation tool in conscious patients with hemiparesis or cognitive dysfunction.

PURPOSE: Altered cognition or hemiparesis can occur in neurocritical but conscious patients, and recognizing pain is challenging. This study aimed to test the reliability and validity of the Critical-Care Pain Observation Tool (CPOT) in this specific group. MATERIALS AND METHODS: This prospective study included ventilated, conscious patients who had certain neurologic deficits. CPOT scores were assessed before and after nociceptive (turning the patient) and non-nociceptive (measuring body temperature) procedures. The patients' self-reported pain was also recorded using a numerical rating scale (NRS). RESULTS: Sixty-three patients were enrolled. The intraclass correlation coefficient was r = 0.975-1.000 (p < 0.001) for turning the patient. Discriminant validation indicated that CPOT scores were significantly higher after turning the patient compared with measuring body temperature (p = 0.025). CPOT scores were positively correlated with NRS when turning the patient (r = 0.724, p < 0.001). After turning, the mean increase in CPOT score was lower in the patients with hemiparesis than in those without hemiparesis (p = 0.079), however it was significantly higher in the patients with cognitive dysfunction compared to those without cognitive dysfunction (p = 0.022). CONCLUSIONS: The CPOT is an appropriate instrument to assess pain in conscious patients, particularly those with cognitive dysfunction. The influence of hemiparesis on the CPOT is noteworthy.

Interleukin-1ß-induced matrix metalloproteinase-3 via ERK1/2 pathway to promote mesenchymal stem cell migration.

Human umbilical cord Wharton's jelly derived mesenchymal stem cells (hUCMSCs), a source of cell therapy, have received a great deal of attention due to their homing or migrating ability in response to signals emanating from damaged sites. It has been found that IL-1ß possesses the ability to induce the expression of matrix metalloproteinase-3 (MMP-3) in bone marrow MSCs. MMP-3 is involved in cell migration in various types of cells, including glioblastoma, vascular smooth muscle, and adult neural progenitor cells. In this study, we proposed that IL-1ß influences hUCMSCs migration involving MMP-3. The expression level of MMP-3 in IL-1ß-induced hUCMSCs was verified using cDNA microarray analysis, quantitative real-time PCR, ELISA and Western blot. Wound-healing and trans-well assay were used to investigate the cell migration and invasion ability of IL-1ß-treated hUCMSCs. In addition, we pre-treated hUCMSCs with interleukin-1 receptor antagonist, MMP-3 inhibitors (ALX-260-165, UK 356618), or transfected with MMP-3 siRNA to confirm the role of MMP3 in IL-1ß-induced cell migration. Our results showed that IL-1ß induced MMP-3 expression is related to the migration of hUCMSCs. Moreover, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126, p38 inhibitor SB205380, JNK inhibitor SP600125 and Akt inhibitor GSK 690693 decreased IL-1ß-induced MMP-3 mRNA and protein expression. The migration and invasion ability analyses showed that these inhibitors attenuated the IL-1ß-induced migration and invasion ability of hUCMSCs. In conclusion, we have found that IL-1ß induces the expression of MMP-3 through ERK1/2, JNK, p38 MAPK and Akt signaling pathways to enhance the migration of hUCMSCs. These results provide further understanding of the mechanisms in IL-1ß-induced hUCMSCs migration to injury sites.

Flow density of computed tomography aortography for predicting early unfavorable aortic remodeling after TEVAR in type IIIb aortic dissection.

OBJECTIVE: Patients diagnosed of DeBakey type III aortic dissection with partial thrombosis of false lumen (FL) have a higher mortality rate. However, IIIb dissections with full patent FL tend to exhibit a partially thrombosed FL quickly after thoracic endovascular aortic repair (TEVAR); thus, we investigated survival and aortic remodeling in this population. METHODS: We reviewed computed tomography aortograms (CTAs) of 123 patients with TEVAR-treated IIIb aortic dissections from July 2006 to June 2015; contrast density of CTAs represented intraluminal flow. Patients were selected to fit in 2 groups of FL in term of FL contrast density: low flow (LF) group (non-opacification in the midway of FL) and high flow (HF) group (full patent FL). RESULTS: Surgical mortality was 10.3% in the HF group and 4.5% in the LF group (n = 61; LF = 22; HF = 39). 3 patients in the HF group suffered from lethal aortic rupture in 10 days postoperatively. The HF group showed significant increase in maximal diameter, and had larger thoracic (+4.00 ± 2.68 vs -1.16 ± 3.42 mm, P < .001) aortic diameter expansion from preoperation to one week postoperation. Both groups exhibited significant favorable thoracic TL expansion and maximal aortic diameter shrinkage in postoperative one week to one year. However, HF group displayed less thoracic aortic FL regression (-70.9 ± 83.5 vs -113.9 ± 95.0 cm3, P = .1) and TL expansion (+14.5 ± 27.2 vs +36.8 ± 28.3 cm3, P = .008) when compared to LF group. CONCLUSIONS: Preoperative HF in the FL has an unfavorable effect on thoracic aortic diameter in one week post-TEVAR. This might increase the risk of aortic rupture.

Evaluation of a Community-Run and General-Practitioner-Supervised Self-Care for Minor Illnesses (CGPSC) Program in a Remote Area in Taiwan.

Although Taiwanese citizens benefit from affordable health care, residents in remote areas extensively rely on unsafe self-care practices because of a lack of easy access to medical services. To improve self-care safety, ten easy-access self-care medical spots (ESCMSs) managed by trained residents were established in two remote villages. This study aimed to assess the impact of ESCMSs on self-care and access to medical services. For a total of six commonly experienced minor illnesses, the average number of illnesses for which residents were confident to perform self-care increased from 2.78 in the pretest to 3.58 in the post-test. ESCMSs were also the first choice when experiencing minor illnesses for 31.25% residents who did not visit a doctor. Residents' personal experience with ESCMSs correlated with their perception of ESCMSs' function. Compared with residents who had no personal experience of using ESCMSs, those who used the ESCMS service were less likely to store medications for minor illnesses at home (51.02% vs. 76.67%). Furthermore, those who attribute the reduced needs for professional help to ESCMSs had used medications for minor illnesses at ESCMSs. These results suggest that establishing ESCMSs is a viable alternative to increase the self-care capacity of residents in remote areas and increase the access to medical resources. Moreover, because residents are less likely to store medication and travel for professional help, ESCMSs could indirectly reduce the risks of self-medication and traffic accidents, respectively. However, caution should be exercised when generalizing these results to more populated areas that also lack medical resources.

Follicular Graft-versus-host Disease: A Rare Manifestation in a Patient with the Overlap Subtype of Chronic Graft-versus-host Disease.

Graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Although skin involvement is common, generalized follicular eruption as the major clinical manifestation is rare. However, it is important for clinicians to recognize it at the earliest to initiate an appropriate therapy. We report a case of a patient with multiple myeloma who developed extensive hyperkeratotic, lichenoid folliculocentric papules with perifollicular erythema on day 53 following an allogeneic HSCT. The overall clinical and histological findings were consistent with the overlap subtype of chronic follicular GVHD.

Revealing hidden spin-momentum locking in a high-temperature cuprate superconductor.

Cuprate superconductors have long been thought of as having strong electronic correlations but negligible spin-orbit coupling. Using spin- and angle-resolved photoemission spectroscopy, we discovered that one of the most studied cuprate superconductors, Bi2212, has a nontrivial spin texture with a spin-momentum locking that circles the Brillouin zone center and a spin-layer locking that allows states of opposite spin to be localized in different parts of the unit cell. Our findings pose challenges for the vast majority of models of cuprates, such as the Hubbard model and its variants, where spin-orbit interaction has been mostly neglected, and open the intriguing question of how the high-temperature superconducting state emerges in the presence of this nontrivial spin texture.

Interleukin-1ß induces CXCR3-mediated chemotaxis to promote umbilical cord mesenchymal stem cell transendothelial migration.

BACKGROUND: Mesenchymal stem cells (MSCs) are known to home to injured and inflamed regions via the bloodstream to assist in tissue regeneration in response to signals of cellular damage. However, the factors and mechanisms that affect their transendothelial migration are still unclear. In this study, the mechanisms involved in interleukin-1ß (IL-1ß) enhancing the transendothelial migration of MSCs were investigated. METHODS: Immunofluorescence staining and Western blotting were used to observe IL-1ß-induced CXC chemokine receptor 3 (CXCR3) expression on MSCs. Quantitative real-time PCR and ELISA were used to demonstrate IL-1ß upregulated both chemokine (C-X-C motif) ligand 9 (CXCL9) mRNA and CXCL9 ligand secretion in human umbilical vein endothelial cells (HUVECs). Monolayer co-cultivation, agarose drop chemotaxis, and transwell assay were conducted to investigate the chemotaxis invasion and transendothelial migration ability of IL-1ß-induced MSCs in response to CXCL9. RESULTS: In this study, our immunofluorescence staining showed that IL-1ß induces CXCR3 expression on MSCs. This result was confirmed by Western blotting. Following pretreatment with protein synthesis inhibitor cycloheximide, we found that IL-1ß induced CXCR3 on the surface of MSCs via protein synthesis pathway. Quantitative real-time PCR and ELISA validated that IL-1ß upregulated both CXCL9 mRNA and CXCL9 ligand secretion in HUVECs. In response to CXCL9, chemotaxis invasion and transendothelial migration ability were increased in IL-1ß-stimulated MSCs. In addition, we pretreated MSCs with CXCR3 antagonist AMG-487 and p38 MAPK inhibitor SB203580 to confirm CXCR3-CXCL9 interaction and the role of CXCR3 in IL-1ß-induced chemotaxis invasion and transendothelial migration. CONCLUSION: We found that IL-1ß induces the expression of CXCR3 through p38 MAPK signaling and that IL-1ß also enhances CXCL9 ligand secretion in HUVECs. These results indicated that IL-1ß promotes the transendothelial migration of MSCs through CXCR3-CXCL9 axis. The implication of the finding could enhance the efficacy of MSCs homing to target sites.

IL-1ß-Induced Matrix Metalloprotease-1 Promotes Mesenchymal Stem Cell Migration via PAR1 and G-Protein-Coupled Signaling Pathway.

Mesenchymal stem cells (MSCs) are known for homing to sites of injury in response to signals of cellular damage. However, the mechanisms of how cytokines recruit stem cells to target tissue are still unclear. In this study, we found that the proinflammation cytokine interleukin-1ß (IL-1ß) promotes mesenchymal stem cell migration. The cDNA microarray data show that IL-1ß induces matrix metalloproteinase-1 (MMP-1) expression. We then used quantitative real-time PCR and MMP-1 ELISA to verify the results. MMP-1 siRNA transfected MSCs, and MSC pretreatment with IL-1ß inhibitor interleukin-1 receptor antagonist (IL-1RA), MMP tissue inhibitor of metalloproteinase 1 (TIMP1), tissue inhibitor of metalloproteinase 2 (TIMP2), MMP-1 inhibitor GM6001, and protease-activated receptor 1 (PAR1) inhibitor SCH79797 confirms that PAR1 protein signaling pathway leads to IL-1ß-induced cell migration. In conclusion, IL-1ß promotes the secretion of MMP-1, which then activates the PAR1 and G-protein-coupled signal pathways to promote mesenchymal stem cell migration.

Piperacillin-Tazobactam-Induced Linear IgA Bullous Dermatosis Supported by a T-Cell Activation Assay.

Linear immunoglobulin (Ig) A bullous dermatosis (LABD) is a rare subepidermal autoimmune blistering disease characterized by linear IgA deposits at the basement membrane zone visualized with direct immunofluorescence (DIF). Most cases of LABD are idiopathic, but some are drug-induced with vancomycin being the most common causative agent. We herein report a patient presenting with blisters and erosive lesions, primarily in the intertriginous and flexor areas, consistent with a diagnosis of piperacillin-tazobactam-induced LABD based on the patient's clinical course and histopathology, DIF, and in vitro T-cell activation assay (TAA) findings. Only one case of piperacillin-tazobactam-induced LABD has been previously reported. In addition to its rarity, our case was also unique in that the skin lesions occurred in the intertriginous and flexor areas, uncommon locations for typical adult patients with LABD, and TAA strongly suggested an association with the causative drug.

A facile novel fluorocarbon copolymer solution coating process for improving platelet compatibility of titanium.

Titanium (Ti) and its alloys possess mechanical properties that are desirable in many biomedical applications compared to other metals. Furthermore, the native metal oxide layer that prevents further oxidation is also known to be biocompatible. However, clinical findings have shown that titanium and its alloys are prone to adverse bioreactions such as platelet adhesion and activation which could lead to thrombogenic complications. It has been found that surfaces modified with fluorocarbons could reduce the degree of both platelet adhesion and activation. Nevertheless, direct fluorocarbon deposition onto titanium substrates would require significant technical efforts. Instead, this research utilized a facile coating process with novel copolymers containing 2,2,2-trifluoroethyl methacrylate (TFEMA) and vinylphosphonic acid (VPA) to modify the titanium surface, giving the surface lower surface energy and higher hydrophobicity, significantly reducing the thrombus formation while exhibiting good cytocompatibility. The anchorage group, phosphonic acid provided by VPA, can be covalently bound to the oxide surface of titanium metal. Via free radical polymerization, VPA and TFEMA formed copolymers with different hydrophobicity were then used to modify titanium substrates, on which a series of surface characterization, in vitro platelet adhesion tests, and cytotoxicity assays were performed. Nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) confirmed the synthesis of the copolymers and the modification of Ti substrates. The platelet adhesion tests showed significantly reduced amount of adherent platelets on certain copolymer-modified Ti substrates with low degrees of activation. The in vitro cytotoxicity assays further highlighted that the modifications conducted on Ti does not induce cytotoxicity.

Comorbid autoimmune diseases in patients with pemphigus: a nationwide case-control study in Taiwan.

Previous studies have proposed the association between pemphigus and several autoimmune diseases, but no large-scale study has been reported. To delineate the association between pemphigus and autoimmune diseases including psoriasis. A total of 1,998 patients with pemphigus and 7,992 control subjects were enrolled from the National Health Insurance Research Database in Taiwan from 1997 to 2010. The odds of comorbidities between these two groups were analysed by multivariate logistic regression. Compared with control subjects, patients with pemphigus were much more likely to have Sjögren's syndrome (odds ratio [OR]: 15.0; 95% confidence interval [CI]: 3.16-71.5), psoriasis (OR: 7.18; 95% CI: 5.55-9.29), systemic lupus erythematosus (OR: 4.46; 95% CI: 1.88-10.6), and alopecia areata (OR: 2.68; 95% CI: 1.26-5.67). According to gender-stratified analyses, however, the association between pemphigus and Sjögren's syndrome or alopecia areata was found to be significant only in the female patients. We confirm the association between pemphigus and some autoimmune diseases, including Sjögren's syndrome, systemic lupus erythematosus, and alopecia areata. In addition, we present the novel finding that patients with pemphigus have an increased risk of psoriasis.

Molecular Arrangement and Charge Transfer in C60/Graphene Heterostructures.

Charge transfer at the interface between dissimilar materials is at the heart of electronics and photovoltaics. Here we study the molecular orientation, electronic structure, and local charge transfer at the interface region of C60 deposited on graphene, with and without supporting substrates such as hexagonal boron nitride. We employ ab initio density functional theory with van der Waals interactions and experimentally characterize interface devices using high-resolution transmission electron microscopy and electronic transport. Charge transfer between C60 and the graphene is found to be sensitive to the nature of the underlying supporting substrate and to the crystallinity and local orientation of the C60. Even at room temperature, C60 molecules interfaced to graphene are orientationally locked into position. High electron and hole mobilities are preserved in graphene with crystalline C60 overlayers, which has ramifications for organic high-mobility field-effect devices.

Comorbid autoimmune diseases in patients with sarcoidosis: A nationwide case-control study in Taiwan.

The association between sarcoidosis and autoimmune comorbidities has been reported, however, it has seldom been confirmed by a large nationwide study. Our study aimed to clarify the association between sarcoidosis and autoimmune comorbidities in the Taiwanese. A total of 1237 patients with sarcoidosis and 4948 age- and sex-matched control subjects were selected from the National Health Insurance Research Database of Taiwan from 1997 to 2010. Multiple logistic regressions were performed to calculate the odds of comorbidities between the two groups. The prevalence of sarcoidosis was 2.17/100 000 individuals in Taiwan. Sarcoidosis patients tended to run a higher risk of autoimmune comorbidities than the control group (17.6% vs 9.4%, P < 0.05). Autoimmune thyroid disease (adjusted odd ratio [aOR], 1.32; 95% confidence interval [CI], 1.05-1.64), Sjögren's syndrome (aOR, 11.6; 95% CI, 4.36-31.0) and ankylosing spondylitis (aOR, 3.80; 95% CI, 2.42-5.97) were significantly associated with sarcoidosis. The sex-stratified analyses were carried out to demonstrate a significant association of sarcoidosis with ankylosing spondylitis in both sexes, but with autoimmune thyroid disease in male patients and with Sjögren's syndrome female patients, respectively. Besides, the diagnosis of the autoimmune comorbidities strongly associated with sarcoidosis tended to be established after that of sarcoidosis. This study demonstrated that patients with sarcoidosis tended to have autoimmune thyroid disease, Sjögren's syndrome and ankylosing spondylitis, and the diagnosis of sarcoidosis usually preceded that of associated comorbidities. Clinicians should be alert to autoimmune comorbidities in patients with sarcoidosis.

Determinants of High Fasting Insulin and Insulin Resistance Among Overweight/Obese Adolescents.

Hyperinsulinaemia is the earliest subclinical metabolic abnormality, which precedes insulin resistance in obese children. An investigation was conducted on the potential predictors of fasting insulin and insulin resistance among overweight/obese adolescents in a developing Asian country. A total of 173 overweight/obese (BMI > 85th percentile) multi-ethnic Malaysian adolescents aged 13 were recruited from 23 randomly selected schools in this cross-sectional study. Waist circumference (WC), body fat percentage (BF%), physical fitness score (PFS), fasting glucose and fasting insulin were measured. Insulin resistance was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). Adjusted stepwise multiple regression analysis was performed to predict fasting insulin and HOMA-IR. Covariates included pubertal stage, socioeconomic status, nutritional and physical activity scores. One-third of our adolescents were insulin resistant, with girls having significantly higher fasting insulin and HOMA-IR than boys. Gender, pubertal stage, BMI, WC and BF% had significant, positive moderate correlations with fasting insulin and HOMA-IR while PFS was inversely correlated (p < 0.05). Fasting insulin was primarily predicted by gender-girls (Beta = 0.305, p < 0.0001), higher BMI (Beta = -0.254, p = 0.02) and greater WC (Beta = 0.242, p = 0.03). This study demonstrated that gender, BMI and WC are simple predictors of fasting insulin and insulin resistance in overweight/obese adolescents.