The adjusted impact of different severities of acute exacerbations and medications on the risk of developing dementia in COPD patients.

BACKGROUND: Although a relationship between chronic obstructive pulmonary disease (COPD) and dementia has been reported, the initial severity upon emergency department (ED) visits and the medications used have not been well evaluated as risk factors for increased dementia occurrence. We aimed to analyze the risks of dementia development over 5 years among patients with COPD compared to matched controls (primary) and the impact of different severities of acute exacerbations (AEs) of COPD and medications on the risk of dementia development among COPD patients (secondary). METHOD: This study used the Taiwanese government deidentified health care database. We enrolled patients during the 10-year study period (January 1, 2000, to December 31, 2010), and each patient was followed up for 5 years. Once these patients received a diagnosis of dementia or died, they were no longer followed up. The study group included 51,318 patients who were diagnosed with COPD and 51,318 matched (in terms of age, sex, and the number of hospital visits) non-COPD patients from the remaining patients as the control group. Each patient was followed up for 5 years to analyze the risk of dementia with Cox regression analysis. Data on medications (antibiotics, bronchodilators, corticosteroids) and severity at the initial ED visit (ED treatment only, hospital admission, or ICU admission) were collected for both groups, as well as demographics and baseline comorbidities, which were considered confounding factors. RESULTS: In the study and control groups, 1,025 (2.0%) and 423 (0.8%) patients suffered from dementia, respectively. The unadjusted HR for dementia was 2.51 (95% CI: 2.24-2.81) in the study group. Bronchodilator treatment was associated with the HRs, especially among those who received long-term (> 1 month) treatment (HR = 2.10, 95% CI: 1.91-2.45). Furthermore, among 3,451 AE of COPD patients who initially visited the ED, patients who required ICU admission (n = 164, 4.7%) had a higher risk of dementia occurrence (HR = 11.05, 95% CI: 7.77-15.71). CONCLUSION: Bronchodilator administration might be associated with a decreased risk of dementia development. More importantly, patients who suffered AEs of COPD and initially visited the ED and required ICU admission had a higher risk of developing dementia.

Result of cementless total hip arthroplasty in a patient with osteopoikilosis, hip dysplasia and advanced osteoarthritis: a case report.

BACKGROUND: Osteopoikilosis (OPK) is a rare benign sclerosing bone dysplasia and is often incidentally found on plain radiography. OPK generally does not require treatment. Nevertheless, osteonecrosis or degenerative joint disease can occur in the setting of OPK, and little is known with regard to the longevity of arthroplasty prostheses implanted into OPK-bearing bones. CASE PRESENTATION: A 55-year-old male presented with progressive right hip pain in 2012. He was diagnosed with coexisting osteopoikilosis and developmental dysplasia of the right hip with advanced osteoarthritis after a series of imaging studies including radiographs, magnetic resonance imaging (MRI), and bone scan. A cementless total hip arthroplasty was performed to treat his right hip pain. Radiographs at eight-year follow-up showed the prosthetic components were well-fixed. Harris hip score of the patient's right hip was 93. The patient can walk without assistance and work as a construction worker. CONCLUSION: Cementless arthroplasty can be considered in patients with hip arthropathies and co-existing osteopoikilosis. Continued follow-up is required to establish the long-term results.

The favorable outcome of Bernese periacetabular osteotomy for the hip osteoarthritis in multiple epiphyseal dysplasia.

BACKGROUND: Multiple epiphyseal dysplasia (MED) is a rare congenital bone dysplasia. Patients with MED develop secondary hip osteoarthritis as early as the third to the fourth decade. Currently, there is no consensus on the prevention of the progressive hip osteoarthritis secondary to MED. The Bernese periacetabular osteotomy (PAO) is a joint-preserving surgery to reshape acetabulum and extend femoral head coverage. However, there is no documentary evidence for the effect of the procedure on MED hips. PATIENTS AND METHODS: We analyzed the preliminary outcomes following the Bernese PAO in 6 MED hips. The average age at the time of surgery was 14.3 years (range from 11.4 to 17.2 years). For our study interest of time efficiency, radiographic parameters were analyzed preoperatively and 1 year postoperatively. The hip function was evaluated by the Harris Hip Score (HHS) before and after surgery. RESULTS: The mean follow-up time was 1.7 years. The mean lateral center-edge angle increased from 3.8° to 47.1° (p = 0.02), anterior center-edge angle increased from 7.3° to 35.1° (p = 0.02), and acetabulum index decreased from 27.8° to 14.6° (p = 0.04). The femoral head coverage ratio increased from 66.8% to 100% (p = 0.02). The post-operative anteroposterior pelvic radiograph demonstrated all preoperative broken Shenton lines were reversed. The mean HHS improved from 67.3 to 86.7 (p = 0.05). CONCLUSION: Bernese PAO is a feasible treatment for hip disorders in MED patients. It reshapes acetabular and femoral morphology efficiently. In our study, the preliminary results showed the procedure not only improved radiographic outcomes but also hip function.

2,3,5,4'-Tetrahydroxystilbene (TG1), a Novel Compound Derived from 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (THSG), Inhibits Colorectal Cancer Progression by Inducing Ferroptosis, Apoptosis, and Autophagy.

BACKGROUND: Colorectal cancer (CRC) is one of the deadliest cancers worldwide and long-term survival is not guaranteed in metastatic disease despite current multidisciplinary therapies. A new compound 2,3,5,4'-Tetrahydroxystilbene (TG1), derived from THSG (2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside), has been developed, and its anticancer ability against CRC is verified in this study. METHODS: HCT116, HT-29, and DLD-1 were treated with TG1 and the IC50 was measured using a sulforhodamine B assay. A Xenograft mouse model was used to monitor tumor growth. Apoptosis and autophagy, induced by TG1 in CRC cells, were examined. RNA-sequencing analysis of CRC cells treated with TG1 was performed to discover underlying pathways and mechanisms. RESULTS: The results demonstrated that treatment with TG1 inhibited CRC proliferation in vitro and in vivo and induced apoptotic cell death, which was confirmed by Annexin V-FITC/PI staining and Western blotting. Additionally, TG1 treatment increased the level of autophagy in cells. RNA-sequencing and GSEA analyses revealed that TG1 was associated with MYC and the induction of ferroptosis. Furthermore, the ferroptosis inhibitor Bardoxolone abrogated the cytotoxic effect of TG1 in CRC cells, indicating that ferroptosis played a crucial role in TG1-induced cytotoxicity. CONCLUSIONS: These findings suggest that TG1 might be a potential and potent compound for clinical use in the treatment of CRC by inhibiting proliferation and inducing ferroptosis through the MYC pathway.

Stepwise formation of iridium(III) complexes with monocyclometalating and dicyclometalating phosphorus chelates.

With the motivation of assembling cyclometalated complexes without nitrogen-containing heterocycle, we report here the design and systematic synthesis of a class of Ir(III) metal complexes functionalized with facially coordinated phosphite (or phosphonite) dicyclometalate tripod, together with a variety of phosphine, chelating diphosphine, or even monocyclometalate phosphite ancillaries. Thus, treatment of [IrCl(3)(tht)(3)] with stoichiometric amount of triphenylphosphite (or diphenyl phenylphosphonite), two equiv of PPh(3), and in presence of NaOAc as cyclometalation promoter, gives formation of respective tripodal dicyclometalating complexes [Ir(tpit)(PPh(3))(2)Cl] (2a), [Ir(dppit)(PPh(3))(2)Cl] (2b), and [Ir(dppit)(PMe(2)Ph)(2)Cl] (2c) in high yields, where tpitH(2) = triphenylphosphite and dppitH(2) = diphenyl phenylphosphonite. The reaction sequence that afforded these complexes is established. Of particular interest is isolation of an intermediate [Ir(tpitH)(PPh(3))(2)Cl(2)] (1a) with monocyclometalated phosphite, together with the formation of [Ir(tpit)(tpitH)(PPh(3))] (3a) with all tripodal, bidentate, and monodentate phosphorus donors coexisting on the coordination sphere, upon treatment of 2a with a second equiv of triphenylphosphite. Spectroscopic studies were performed to explore the photophysical properties. For all titled Ir(III) complexes, virtually no emission can be observed in either solution at room temperature or 77 K CH(2)Cl(2) matrix. Time-dependent DFT calculation indicates that the lowest energy triplet manifold involves substantial amount of metal centered (3)MC dd contribution. Due to its repulsive potential energy surface (PES) that touches the PES of ground state, the (3)MC dd state executes predominant nonradiative deactivation process.

Geometric incision design for reduction nippleplasty.

BACKGROUND: Nipple hypertrophy is a frequently encountered problem in Asian women. It may be congenital or caused by hormones, breast feeding, or gestation. The hypertrophy has been linked primarily to aesthetics. The nipples of Asian women usually are 6-10 mm in diameter and 5-8 mm in height, and women with nipples larger than 1.5 cm in diameter or height frequently ask for reduction nippleplasty. METHODS: Women with nipple hypertrophy seeking reductive surgery at the authors' hospital between 2004 and 2009 were considered for nippleplasty. A new design consisting of three dermal flaps and sparing of the central column was used. This design can reduce the diameter, height, and most importantly, the basal shape of the nipple without compromising neurovascular supply and functions. RESULTS: During the aforementioned period, 86 nipples of 43 patients were corrected with this method. All the patients were satisfied with the aesthetic results, preserved lactation, and sensory function. No major complications such as necrosis, infection, or numbness of the nipple occurred. CONCLUSIONS: This reduction nippleplasty method can be applied for all types of nipple hypertrophy to create a new nipple of the desired height and diameter without significant complications.

Development of Irinotecan Liposome Armed with Dual-Target Anti-Epidermal Growth Factor Receptor and Anti-Fibroblast Activation Protein-Specific Antibody for Pancreatic Cancer Treatment.

Pancreatic cancer is one of the most common causes of death in Taiwan. Previous studies have shown that more than 90% of pancreatic cancer cells presented epidermal growth factor receptor (EGFR) cell marker, and this marker is thought to be important as it is related to activation of cancer cell proliferation, angiogenesis, and cancer progression. Moreover, tumor-associated fibroblasts were involved in tumor proliferation and progression. In this study, we fabricated an anti-EGFR and anti-fibroblast activation protein bispecific antibody-targeted liposomal irinotecan (BS-LipoIRI), which could specifically bind to pancreatic cancer cells and tumor-associated fibroblasts. The drug encapsulation efficiency of BS-LipoIRI was 80.95%, and the drug loading was 8.41%. We proved that both pancreatic cancer cells and fibroblasts could be targeted by BS-LipoIRI, which showed better cellular uptake efficacy compared to LipoIRI. Furthermore, an in vivo mouse tumor test indicated that BS-LipoIRI could inhibit pancreatic cancer growth up to 46.2% compared to phosphate-buffered saline control, suggesting that BS-LipoIRI could be useful in clinical cancer treatment.

A Selective Histone Deacetylase Inhibitor Induces Autophagy and Cell Death via SCNN1A Downregulation in Glioblastoma Cells.

Glioblastoma multiforme (GBM) is a grade IV, highly malignant brain tumor. Because of the heterogeneity of GBM, a multitarget drug is a rational strategy for GBM treatment. Histone deacetylase inhibitors (HDACis) regulate the expression of numerous genes involved in cell death, apoptosis, and tumorigenesis. We found that the HDAC4/HDAC5 inhibitor LMK235 at 0.5 µM significantly reduced the cell viability and colony formation of patient-derived, temozolomide-resistant GBM P#5 TMZ-R, U-87 MG, and T98G cells. Moreover, LMK235 also significantly increased TUBA acetylation, which is an indicator of HDAC inhibition. Interestingly, LMK235 induced MAP1LC3 robust readout and puncta accumulation but did not enhance PARP1 cleavage or the proportion of annexin V-positive cells, suggesting that LMK235-induced cell death occurred via autophagy activation. Further RNA-seq analysis after LMK235 treatment showed that 597 different expression genes compared to control. After bioinformatic analysis by KEGG and STRING, we focused on 34 genes and validated their mRNA expression by qPCR. Further validation showed that 2 µM LMK235 significantly reduced the mRNA and protein expression of SCNN1A. Cell viability of SCNN1A-silenced cells were reduced, but cells were rescued while treated with an autophagy inhibitor bafilomycin A1. Conclusively, SCNN1A plays a role in LMK235-induced autophagy and cell death in GBM cells.

Emissive iridium(III) diimine complexes formed by double cyclometalation of coordinated triphenylphosphite.

We report on the synthesis of a new series of iridium(III) complexes functionalized with various diimine chromophores, together with a facially coordinated dicyclometalated phosphite chelate and a monodentate anionic ancillary. This conceptual design presents a novel strategy in obtaining a new class of iridium(III) diimine complexes without employment of traditional nitrogen-containing polyaromatic cyclometalates. Additionally, we discuss the basic charactersistics of the ground and lower-lying excited states involved, as documented by crystal structural, photophysical studies, and density functional theory calculations. Fabrication of the green-emitting organic light-emitting diodes with one such dopant, [Ir(dbbpy)(tpit)NCS] (2b), where dbbpy and tpit represent di-tert-butyl-2,2'-bipyridine and dicyclometalated triphenylphosphite, respectively, was successfully made, attaining a peak external quantum efficiency (η(ext)), a luminance efficiency (η(l)), and a power efficiency (η(p)) of 14.1%, 46.6 cd A(-1), and 39.9 lm W(-1), respectively.

Reduction of breast tumor drug resistance by 2,3,5,4'-tetrahydroxystilbene for exhibition synergic chemotherapeutic effect.

Chemotherapy drugs have limited efficacy in breast cancer due to multidrug resistance generated by cancer cells against anticancer drugs. In this study, we developed a novel derivative, 2, 3, 5, 4'-tetrahydroxystilbene (TG1) by modifying 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG). In-vivo zebrafish embryo tests revealed that TG1 showed low toxicity. The equitoxic combination of DOX or DTX with TG1 in MCF-7/Adr reduced the IC50 of DOX or DTX, and the combination index (CI) showed strong synergistic effects in the 1:3 molar ratio of DTX: TG1 and 1:5 molar ratio of DOX: TG1. Moreover, fluorescence images confirmed the cellular uptake of DOX when combined with TG1 in MCF-7/Adr. Western blotting analysis indicated downregulation of p-glycoprotein (P-gp) after MCF-7/Adr treated with TG1. In conclusion, the combined therapy of DTX or DOX and TG1 increases drug efficacy via suppressing the p-glycoprotein efflux pump. These results suggest that TG1 may have potential use for breast cancer patients, especially those with multidrug resistance.

Development of Decellularized Cornea by Organic Acid Treatment for Corneal Regeneration.

IMPACT STATEMENT: This study successfully developed decellularized corneal scaffolds that were prepared by organic acid, which safely exist in animal tissues and plants. The results showed the highly efficient removal of cell debris from porcine corneas, and excellent preservation of optical properties, extracellular matrix (ECM) architecture, and biomolecules. In addition, decellularized corneal scaffolds revealed excellent biocompatibility and recellularization potential in vitro. In an animal model, the transplanted corneas were completely epithelialized, clear, showed no signs of immune response, and effectively supported stromal keratocytes growth. Hence, this could be a promising scaffold material for corneal tissue engineering applications.

Consensus Recommendations for Optimal Augmentation of the Asian Face with Hyaluronic Acid and Calcium Hydroxylapatite Fillers.

BACKGROUND: Although the use of filling agents for soft-tissue augmentation has increased worldwide, most consensus statements do not distinguish between ethnic populations. There are, however, significant differences between Caucasian and Asian faces, reflecting not only cultural disparities, but also distinctive treatment goals. Unlike aesthetic patients in the West, who usually seek to improve the signs of aging, Asian patients are younger and request a broader range of indications. METHODS: Members of the Asia-Pacific Consensus group-comprising specialists from the fields of dermatology, plastic surgery, anatomy, and clinical epidemiology-convened to develop consensus recommendations for Asians based on their own experience using cohesive polydensified matrix, hyaluronic acid, and calcium hydroxylapatite fillers. RESULTS: The Asian face demonstrates differences in facial structure and cosmetic ideals. Improving the forward projection of the "T zone" (i.e., forehead, nose, cheeks, and chin) forms the basis of a safe and effective panfacial approach to the Asian face. Successful augmentation may be achieved with both (1) high- and low-viscosity cohesive polydensified matrix/hyaluronic acid and (2) calcium hydroxylapatite for most indications, although some constraints apply. CONCLUSION: The Asia-Pacific Consensus recommendations are the first developed specifically for the use of fillers in Asian populations. CLINCIAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Accurate surface tension measurement of glass melts by the pendant drop method.

A pendant drop tensiometer, coupled with image digitization technology and a best-fitting algorithm, was built to accurately measure the surface tension of glass melts at high temperatures. More than one thousand edge-coordinate points were obtained for a pendant glass drop. These edge points were fitted with the theoretical drop profiles derived from the Young-Laplace equation to determine the surface tension of glass melt. The uncertainty of the surface tension measurements was investigated. The measurement uncertainty (σ) could be related to a newly defined factor of drop profile completeness (Fc): the larger the Fc is, the smaller σ is. Experimental data showed that the uncertainty of the surface tension measurement when using this pendant drop tensiometer could be ±3 mN∕m for glass melts.

A simple method for measuring the superhydrophobic contact angle with high accuracy.

A modified selected-plane method for contact angle (theta) measurement is proposed in this study that avoids the difficulty of finding the real contact point and image-distortion effects adjacent to the contact point. This method is particularly suitable for superhydrophobic surfaces. The sessile-drop method coupled with the tangent line is the most popular method to find the contact angle in literature, but it entails unavoidable errors in determining the air-solid base line due to the smoothness problem and substrate tilting. In addition, the tangent-line technique requires finding the actual contact point. The measurement error due to the base line problem becomes more profound for superhydrophobic surfaces. A larger theta deviation results from a more superhydrophobic surface with a fixed base line error. The proposed modified selected-plane method requires only four data points (droplet apex, droplet height, and two interfacial loci close to the air-solid interface), avoiding the problem of the sessile-drop-tangent method in finding the contact point and saving the trouble of the sessile-drop-fitting method for best fitting of the numerous edge points with the theoretical profile. A careful error analysis was performed, and a user-friendly program was provided in this work. This method resulted in an accurate theta measurement and a method that was much improved over the classical selected plane and the sessile-drop-tangent methods. The theta difference between this method and the sessile-drop-fitting method was found to be less than three degrees.