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Purpose Recent studies have revealed that the expression of cancer-associated fibroblast (CAF) activation biomarkers in cancer cells is associated with clinical outcomes in patients with certain types of malignant tumors. However, whether the expression of CAF activation biomarkers affects the prognosis of colorectal cancer (CRC) has not been fully elucidated. This study aimed to evaluate the association between the expression of CAF activation biomarkers in cancer cells with cancer invasion and long-term oncological outcomes in patients with CRC. Methods Cancer specimens obtained from 135 patients with stage I–III CRC were examined using immunohistochemical staining to evaluate the expression of fibroblast specific protein-1 (FSP-1), fibroblast activation protein α (FAPα), α-smooth muscle actin (α-SMA), and vimentin in cancer cells. Results FSP-1 expression in cancer cells was significantly associated with lymphatic invasion, perineural invasion, tumor (T) status, and lymph node (N) status. FAPα expression in cancer cells was significantly associated with lymphatic invasion. On univariate and multivariate analyses, FSP-1 and α-SMA expression in cancer cells were associated with a short 10-year overall survival (OS) and high 10-year systemic recurrence (SR), respectively. Tumor budding was associated with a short 10-year OS. However, FAPα and vimentin did not contribute to the prognosis in this study. Conclusion In this study, we found that FSP-1 expression in cancer cells was related to cancer invasion. Additionally, FSP-1 and α-SMA expression in cancer cells was associated with 10-year OS and SR, respectively. Therefore, these markers may be used as predictors of long-term oncological outcomes in patients with CRC.

Abstract Background Coronary artery disease is a cardiovascular disease with a high mortality and mortality rate in modern society. Vascular stent insertion to restore blood flow is essential to treat this disease. A fully biodegradable vascular scaffold (BVS) is a vascular poly (L-lactic acid) (PLLA) stent that is receiving growing interest as this is biodegradable in the body and does not require secondary removal surgery. However, acidic byproducts composed of PLLA produced during the biodegradation of the BVS can induce an inflammatory response. Magnesium hydroxide, a basic inorganic particle, neutralizes the acidic byproducts of PLLA. Methods In this study, we investigated using a BVS coated with everolimus and surface-modified magnesium hydroxide that suppresses smooth muscle cell proliferation and protects endothelial cells, respectively. The various characteristics of the functional stent were evaluated using in vitro and in vivo analyses. Results The BVS was successfully prepared with evenly coated everolimus and surface-modified magnesium hydroxide. A neutral pH value was maintained by magnesium hydroxide during degradation, and everolimus was released for one month. The coated BVS effectively inhibited protein adsorption and platelet adhesion, demonstrating excellent blood compatibility. In vitro analysis showed that BVS protects endothelial cells with magnesium hydroxide and selectively inhibits smooth muscle cell proliferation via everolimus treatment. The functional BVS was inserted into porcine coronary arteries for 28 days, and the results demonstrated that the restenosis and inflammation greatly decreased and re-endothelialization was enhanced as compared to others. Conclusions This study provides new insights into the design of drug-incorporated BVS stent for coronary artery disease. Graphical Abstract

Objective Putaminal iron deposition is an important feature that helps differentiate multiple system atrophy with predominant parkinsonism (MSA-p) from Parkinson’s disease (PD). Most previous studies used visual inspection or quantitative methods with manual manipulation to perform this differentiation. We investigated the value of a new semiautomated diagnostic algorithm using 3T-MR susceptibility-weighted imaging for MSA-p. Methods This study included 26 MSA-p, 68 PD, and 41 normal control (NC) subjects. The algorithm was developed in 2 steps: 1) determine the image containing the remarkable putaminal margin and 2) calculate the phase-shift values, which reflect the iron concentration. The next step was to identify the best differentiating conditions among several combinations. The highest phase-shift value of each subject was used to assess the most effective diagnostic set. Results The raw phase-shift values were present along the lateral margin of the putamen in each group. It demonstrates an anterior-to-posterior gradient that was identified most frequently in MSA-p. The average of anterior 5 phase shift values were used for normalization. The highest area under the receiver operating characteristic curve (0.874, 80.8% sensitivity, and 86.7% specificity) of MSA-p versus PD was obtained under the combination of 3 or 4 vertical pixels and one dominant side when the normalization methods were applied. In the subanalysis for the MSA-p patients with a longer disease duration, the performance of the algorithm improved. Conclusion This algorithm detected the putaminal lateral margin well, provided insight into the iron distribution of the putaminal rim of MSA-p, and demonstrated good performance in differentiating MSA-p from PD.

Abstract Pigs are important experimental animals for cardiovascular research. Few porcine coronary atherosclerosis models have been developed; however, their induction requires more than six months. We developed a porcine coronary artery atherosclerosis model using nicotine injection with a balloon overdilation. A coronary balloon was placed in the porcine coronary artery and overdilated to induce a mechanical injury. Nicotine was administrated via intramuscular injection every day, and changes in the coronary artery were observed after four weeks. Coronary angiography revealed nicotine injection with a balloon overdilation group showed narrowing of the coronary artery at the injury site. The combination of balloon and nicotine significantly increased the intimal hyperplasia in optical coherence tomography analysis. Proliferated tunica media were noted in the nicotine injection with balloon overdilation groups and lack of collagen was observed in the tunica media at eight weeks. Quantitative analysis showed increased smooth muscle actin alpha (SMA), cluster of differentiation 68 (CD68), and Krüppel-like factor 4 (KLF4) in the nicotine injection with balloon overdilation groups. Immunohistochemistry results showed CD68-positive cells displayed SMA- and KLF4-positive reactivity in the border zone of the intimal hyperplasia. Our results show that nicotine injection with balloon overdilation can induce atherosclerotic lesions within one month, which can serve as an alternative pig animal model for the development of coronary stents.

Cushing syndrome (CS) is rare in pregnancy, and few cases have been reported to date. Women with untreated CS rarely become pregnant because of the ovulatory dysfunction induced by hypercortisolism. It is difficult to diagnose CS in pregnancy because of its very low incidence, the overlap between the clinical signs of hypercortisolism and the physiological changes that occur during pregnancy and the changes in hypothalamus-pituitary-adrenal axis activity that occur during pregnancy and limit the value of standard diagnostic testing. However, CS in pregnancy is associated with poor maternal and fetal outcomes; therefore, its early diagnosis and treatment are important. Here, we report two patients with CS that was not diagnosed during pregnancy, in whom maternal and fetal morbidity developed because of hypercortisolism.

Background: Titanium is commonly used in blood-exposed medical devices because it has superior blood compatibility. Mycophenolic acid inhibits the proliferation of vascular smooth muscle cells. This study examined the effect of a non-polymer TiO2 thin film–coated stent with mycophenolic acid in a porcine coronary overstretch restenosis model.Methods: Thirty coronary arteries in 15 pigs were randomized into three groups in which the coronary arteries were treated with a TiO2 film–coated stent with mycophenolic acid (NTM, n = 10), everolimus-eluting stent with biodegradable polymer (EES, n = 10), or TiO2 film–coated stent (NT, n = 10). A histopathologic analysis was performed 28 days after the stenting.Results: There were no significant intergroup differences in injury score, internal elastic lamina area, or inflammation score. Percent area stenosis was significantly smaller in the NTM and EES groups than in the NT group (36.1 ± 13.63% vs. 31.6 ± 7.74% vs. 45.5 ± 18.96%, respectively, p = 0.0003). Fibrin score was greater in the EES group than in the NTM and NT groups [2.0 (range, 2.0–2.0) vs. 1.0 (range, 1.0–1.75) vs. 1.0 (range, 1.0–1.0), respectively, p < 0.0001]. The in-stent occlusion rate measured by micro-computed tomography demonstrated similar percent area stenosis rates on histology analysis (36.1 ± 15.10% in NTM vs. 31.6 ± 8.89% in EES vs. 45.5 ± 17.26% in NT, p < 0.05).Conclusion: The NTM more effectively reduced neointima proliferation than the NT. Moreover, the inhibitory effect of NTM on smooth muscle cell proliferation was not inferior to that of the polymer-based EES with lower fibrin deposition in this porcine coronary restenosis model.

Heart disease: Coated stents reduce repeated blocking of arteries Coating stents with modified stem cells may reduce the risk of repeated artery blocking in the treatment of heart disease. Currently, tubular stents are used to re-open arteries narrowed or blocked by the build-up of fatty deposits. However, if the artery is damaged by the stent or tries to reject it, the resulting inflammatory immune response can result in restenosis, or re-blocking. Je-Yoel Cho at Seoul National University, Republic of Korea, and co-workers trialed stents coated with modified stem cells in swine models. The stem cells are designed to secrete controlled levels of two growth factors, enabling them to differentiate into blood vessel lining cells and build a protective layer around the stent. In comparison with standard stents and stents coated with unmodified stem cells, the modified stents improved blood flow and reduced restenosis.

In the ship and offshore structure design, age-related problems such as corrosion damage, local denting, and fatigue damage are important factors to be considered in building a reliable structure as they have a significant influence on the residual structural capacity. In shipping, corrosion addition methods are widely adopted in structural design to prevent structural capacity degradation. The present study focuses on the historical trend of corrosion addition rules for ship structural design and investigates their effects on the ultimate strength performance such as hull girder and stiffened panel of double hull oil tankers. Three types of rules based on corrosion addition models, namely historic corrosion rules (pre-CSR), Common Structural Rules (CSR), and harmonised Common Structural Rules (CSRH) are considered and compared with two other corrosion models namely UGS model, suggested by the Union of Greek Shipowners (UGS), and Time-Dependent Corrosion Wastage Model (TDCWM). To identify the general trend in the effects of corrosion damage on the ultimate longitudinal strength performance, the corrosion addition rules are applied to four representative sizes of double hull oil tankers namely Panamax, Aframax, Suezmax, and VLCC. The results are helpful in understanding the trend of corrosion additions for tanker structures.

This study compares the Residual ultimate longitudinal strength – grounding Damage index (R-D) diagrams produced by two analysis methods: the ALPS/HULL Intelligent Supersize Finite Element Method (ISFEM) and the design formula (modified Paik and Mansour) method – used to assess the safety of damaged ships. The comparison includes four types of double-hull oil tankers: Panamax, Aframax, Suezmax and VLCC. The R-D diagrams were calculated for a series of 50 grounding scenarios. The diagrams were efficiently sampled using the Latin Hypercube Sampling (LHS) technique and comprehensively analysed based on ship size. Finally, the two methods were compared by statistically analysing the differences between their grounding damage indices and ultimate longitudinal strength predictions. The findings provide a useful example of how to apply the ultimate longitudinal strength analysis method to grounded ships.

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The standard assessment method for tremor severity in Parkinson's disease is visual observation by neurologists using clinical rating scales. This is, therefore, a subjective rating that is dependent on clinical expertise. The objective of this study was to report clinicians' tendencies to under-rate Parkinsonian tremors in the less affected hand. This was observed through objective tremor measurement with accelerometers. Tremor amplitudes were measured objectively using tri-axis-accelerometers for both hands simultaneously in 53 patients with Parkinson's disease during resting and postural tremors. The videotaped tremor was rated by neurologists using clinical rating scales. The tremor measured by accelerometer was compared with clinical ratings. Neurologists tended to under-rate the less affected hand in resting tremor when the contralateral hand had severe tremor in Session I. The participating neurologists corrected this tendency in Session II after being informed of it. The under-rating tendency was then repeated by other uninformed neurologists in Session III. Kappa statistics showed high inter-rater agreements and high agreements between estimated scores derived from the accelerometer signals and the mean Clinical Tremor Rating Scale evaluated in every session. Therefore, clinicians need to be aware of this under-rating tendency in visual inspection of the less affected hand in order to make accurate tremor severity assessments.

Although there is clinical demand for new technology that can accurately measure Parkinsonian tremors, automatic scoring of Parkinsonian tremors using machine-learning approaches has not yet been employed. This study aims to fill this gap by proposing machine-learning algorithms as a way to predict the Unified Parkinson’s Disease Rating Scale (UPDRS), which are similar to how neurologists rate scores in actual clinical practice. In this study, the tremor signals of 85 patients with Parkinson’s disease (PD) were measured using a wrist-watch-type wearable device consisting of an accelerometer and a gyroscope. The displacement and angle signals were calculated from the measured acceleration and angular velocity, and the acceleration, angular velocity, displacement, and angle signals were used for analysis. Nineteen features were extracted from each signal, and the pairwise correlation strategy was used to reduce the number of feature dimensions. With the selected features, a decision tree (DT), support vector machine (SVM), discriminant analysis (DA), random forest (RF), and k-nearest-neighbor (kNN) algorithm were explored for automatic scoring of the Parkinsonian tremor severity. The performance of the employed classifiers was analyzed using accuracy, recall, and precision, and compared to other findings in similar studies. Finally, the limitations and plans for further study are discussed.

Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day) for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84), and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy.

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT2 receptors (angiotensin II type 2 receptors; AT2R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT2R, with this action being not affected by known ligands of AT2R. This result points towards novel AT2R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.