Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature.

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

Seabuckthorn (Hippophae rhamnoides, L.) pulp oil prevents ultraviolet-induced damage in human fibroblasts.

Seabuckthorn pulp oil (SBO) is used in beauty products because of its rich lipophilic substances with high nutraceutical and cosmeceutical potential. However, the mechanism through which SBO enhances skin elasticity remains unclear. Therefore, in this study, we examined the anti-photoaging activity of SBO in normal human dermal fibroblasts (NHDF) under ultraviolet (UV) irradiation. Pretreatment with SBO significantly suppressed UV-B-induced cell toxicity and collagen degradation, suggesting that SBO contains anti-photoaging substances. Further, palmitoleic acid (POA), the main component of SBO, maintained cell viability and collagen levels in UV-B-irradiated NHDF by suppressing the expression of matrix metalloproteinase 1 (MMP-1) and acted on the inhibition of p38 and JNK phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-κB). These findings suggest the utility of SBO as an anti-photoaging agent.

Coracoclavicular and acromioclavicular ligament reconstruction with a double-bundle semitendinosus autograft and cortical buttons for chronic acromioclavicular joint dislocations: clinical and imaging outcomes.

BACKGROUND: There are few clinical and radiographic studies of coracoclavicular (CC) ligament reconstruction in chronic acromioclavicular (AC) joint dislocation. Additionally, reported AC joint reduction rates vary. HYPOTHESIS: Arthroscopically assisted double-bundle semitendinosus tendon autografts with CC and AC ligament reconstruction for AC joint reconstruction provide AC joint stability and improved function at the final visit. METHODS: In this retrospective study of prospectively collected data, 21 patients surgically treated for chronic AC joint dislocation (Rockwood III-V) were assessed clinically and radiographically preoperatively, and at day 1, 3 months, 12 months, and at a final visit (>24 months) postoperatively. Clinical assessments included Constant and American Shoulder and Elbow Surgeons scores. The CC vertical distance (CCD) on the affected and unaffected sides [CCD ratio (%)] on the anterosuperior view were measured. AC joint vertical reduction loss was defined as an increase in the CCD ratio of >25%. Horizontal AC joint instability was evaluated on axillary views. Pearsons' correlation coefficients were generated to examine the relationships among postoperative clinical scores, CCD ratio, interval from injury to surgery, and age at the time of surgery. RESULTS: Twenty-one shoulders in 21 patients (mean age, 40.0 years at the time of surgery; 16 men, 5 women) were evaluated with a mean 31.7-month follow-up period. The mean Constant scores, American Shoulder and Elbow Surgeons scores, and CCD ratios significantly improved from preoperatively to the final visit (57.4 ± 10.1, 49.1 ± 12.1, 101.6 ± 64.1 preoperatively; 89.6 ± 5.3, 96.5 ± 4.2, 9.9 ± 34.5 at the final visit, respectively [P < .001 for all]). Vertical AC and horizontal AC joint instability were observed in 4 shoulders (19.0%) and in 1 shoulder (4.8%), respectively. However, there was no significant correlation between the increase in CCD and clinical scores at the final visit (Constant score; r = 0.179, P = .438: American Shoulder and Elbow Surgeons score; r = -0.260, P = .256) or the interval from injury to surgery (r = 0.099, P = .669) or age at the time of surgery (r = 0.019, P = .935). No clinical complications were associated with clinical symptoms. CONCLUSIONS: Patients who underwent the index procedure achieved significant improvement in shoulder function without complications related clinical symptom after a mean follow-up interval of 31.7 months. In contrast, the rates of total ACJ instability in the vertical and horizontal planes were unsatisfactory but compatible with those in previous studies.

Subcutaneously Transplanted Fresh Cartilage in Allogeneic and Xenogeneic Immunocompetent Mouse.

Cartilage is considered to be immune privileged in general. Clinically, live cells are removed from subcutaneously transplanted allogeneic cartilage mainly for preservation and for infection control. However, because maintaining cartilage feature requires live chondrocyte, it would be beneficial to subcutaneously transplant cartilage with live chondrocyte even if it was allogeneic. We harvested femoral head from 3-week-old male C57BL/6 mice, subcutaneously transplanted to 6-week-old male mice, BALB/c, BALB/c nu/nu, or C57BL/6-Tg (enhanced green fluorescent protein [EGFP] under the control of the CMV-IE enhancer, chicken beta-actin promoter, rabbit beta-globin genomic DNA [CAG promoter]), as allogeneic, allogeneic immunodeficient control, or syngeneic transplantation. We also transplanted cartilaginous particles from human induced pluripotent stem cells derived from human leukocyte antigen homozygous donor to 6-week-old male mice either BALB/c and BALB/c nu/nu as xenogeneic or xenogeneic immunodeficient control. The transplantation periods were 1, 2, 3, 4, 8, 12, and 24 weeks. As the result, we did not observe exposure of the transplant or apparent macroscopic inflammatory in all samples. Histological analysis suggested that the femoral head showed focal ossification and thinning in syngeneic transplantation. In allogeneic transplantation, slight invasion of CD3 (+) T cell and the denaturation of the cartilage were observed, suggesting immune reaction against allogeneic cartilage. In xenogeneic transplantation, slight invasion of CD3 (+) cell and CD4 (+) cell and the structure of the perichondrium-like tissue got unclear, suggesting slight immune reaction against xenogeneic cartilage. Our findings suggest that we should carefully investigate for appropriate procedure to control immune reaction against allogeneic cartilage with live chondrocyte and to maintain its cartilage feature for long time.

Mitochondrial Transfer Induced by Adipose-Derived Mesenchymal Stem Cell Transplantation Improves Cardiac Function in Rat Models of Ischemic Cardiomyopathy.

Although mesenchymal stem cell transplantation has been successful in the treatment of ischemic cardiomyopathy, the underlying mechanisms remain unclear. Herein, we investigated whether mitochondrial transfer could explain the success of cell therapy in ischemic cardiomyopathy. Mitochondrial transfer in co-cultures of human adipose-derived mesenchymal stem cells and rat cardiomyocytes maintained under hypoxic conditions was examined. Functional recovery was monitored in a rat model of myocardial infarction following human adipose-derived mesenchymal stem cell transplantation. We observed mitochondrial transfer in vitro, which required the formation of cell-to-cell contacts and synergistically enhanced energy metabolism. Rat cardiomyocytes exhibited mitochondrial transfer 3 days following human adipose-derived mesenchymal stem cell transplantation to the ischemic heart surface post-myocardial infarction. We detected donor mitochondrial DNA in the recipient myocardium concomitant with a significant improvement in cardiac function. Mitochondrial transfer is vital for successful cell transplantation therapies and improves treatment outcomes in ischemic cardiomyopathy.

Design of supramolecular hybrid nanomaterials comprising peptide-based supramolecular nanofibers and in situ generated DNA nanoflowers through rolling circle amplification.

The artificial construction of multicomponent supramolecular materials comprising plural supramolecular architectures that are assembled orthogonally from their constituent molecules has attracted growing attention. Here, we describe the design and development of multicomponent supramolecular materials by combining peptide-based self-assembled fibrous nanostructures with globular DNA nanoflowers constructed by the rolling circle amplification reaction. The orthogonally constructed architectures were dissected by fluorescence imaging using the selective fluorescence staining procedures adapted to this study. The present, unique hybrid materials developed by taking advantage of each supramolecular architecture based on their peptide and DNA functions may offer distinct opportunities to explore their bioapplications as a soft matrix.

Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development.

The Runt-related transcription factor (Runx) family plays various roles in the homeostasis of cartilage. Here, we examined the role of Runx2 and Runx3 for osteoarthritis development in vivo and in vitro. Runx3-knockout mice exhibited accelerated osteoarthritis following surgical induction, accompanied by decreased expression of lubricin and aggrecan. Meanwhile, Runx2 conditional knockout mice showed biphasic phenotypes: heterozygous knockout inhibited osteoarthritis and decreased matrix metallopeptidase 13 (Mmp13) expression, while homozygous knockout of Runx2 accelerated osteoarthritis and reduced type II collagen (Col2a1) expression. Comprehensive transcriptional analyses revealed lubricin and aggrecan as transcriptional target genes of Runx3, and indicated that Runx2 sustained Col2a1 expression through an intron 6 enhancer when Sox9 was decreased. Intra-articular administration of Runx3 adenovirus ameliorated development of surgically induced osteoarthritis. Runx3 protects adult articular cartilage through extracellular matrix protein production under normal conditions, while Runx2 exerts both catabolic and anabolic effects under the inflammatory condition.

Intussusception of the cecum due to the acute appendicitis: A case report.

INTRODUCTION AND IMPORTANCE: Intussusception of the cecum due to acute appendicitis is rare condition. PRESENTATION OF CASE: A 17-year-old male patient presented to our hospital with a chief complaint of right lower abdominal pain, which had lasted for two days. Computed tomography (CT) revealed a "target sign" from the cecum to the ascending colon, leading to a diagnosis of cecocolic intussusception. Colonoscopy revealed an erythematous, edematous, and internally distorted cecum in the ascending colon, which was difficult to repair with air insufflation. Laparoscopic surgery was performed to remove the bowel obstruction. Repositioning of the invaginated cecum was difficult due to the presence of a hard and edematous colic wall. Therefore, laparoscopic ileocecal resection was performed to release the obstruction. The pathological diagnosis was appendicitis and abscess within the cecum wall, with no malignant findings. DISCUSSION: In our case, intussusception was considered to have caused thickening of the intestinal wall of the cecum due to inflammation of the appendix, and the thickened area became the leading point. CONCLUSION: Considering that malignancy is a frequent leading point in adult patients with intussusception, a preoperative endoscopic examination is important for minimizing bowel resection.

Seroepidemiological survey of the prevalence of Helicobacter pylori infection in Sabah, Malaysia.

Objective: Gastric cancer is an important cause of mortality in Sabah, Malaysia, but the prevalence of Helicobacter pylori infection in this state is unknown. Serology is an important tool for the surveillance of H. pylori infection. The objective of this study was to determine the prevalence of H. pylori infection by serology, and to provide information for policy discussions on H. pylori control programmes in Sabah. Methods: This cross-sectional study analysed serum samples collected from blood donors in a hospital in Kota Kinabalu, Sabah. H. pylori antibody concentration was measured using a commercially available kit. Results: The prevalence of H. pylori was 28.4% (204/718), and the infection rate was highest in subjects aged 30-39 years. Men were more likely to be infected than women. The H. pylori infection rate was highest among those of Kadazan (19.1%) ethnicity, followed by Dusun (15.7%), Bajau (14.7%) and Rungus (10.8%). Binary logistic regression analysis indicated that Chinese (P=0.026) and Malay (P=0.035) ethnicities were protective against H. pylori infection compared with other ethnicities. Conclusions: The seropositivity rate of H. pylori in this study was similar to the overall seropositivity rate in Malaysia; however, Chinese and Malay ethnicities were found to be protective against H. pylori infection.

Long-term outcomes and duration of outdoor ambulation following primary total knee arthroplasty in patients with rheumatoid arthritis.

BACKGROUND: The medical treatment of rheumatoid arthritis (RA) has made remarkable progress with the introduction of methotrexate and biological agents. However, there have been few reports of long-term results of total knee arthroplasty (TKA) for RA since the introduction of these drugs. Ambulation is an important form of exercise for maintaining health. We investigated the long-term outcomes and the ability to walk outdoors following TKA in patients with RA. METHODS: We retrospectively reviewed 142 patients with RA (201 knees) who had undergone primary TKA. The mean follow-up was 10.6 years. RESULTS: Markers of RA disease activity all improved significantly postoperatively. Mean Japanese Orthopedic Association scores improved from 49.3 points before surgery to 81.8 at follow-up. The mean maximum flexion angle improved from 107.8° to 112.9°. The causes of TKA revision comprised 2 mechanical loosening, 1 late infection, and 1 fracture of the femoral condyle. The survival rate of TKA was 96.6% at 15 years. Fifty-five patients were not able to walk outdoors. The rate of inability to ambulate outdoors was 38.3 per 1000 person-years. The survival rate of ability to ambulate outdoors were 48.8% at 15 years. Preoperative advanced age, low body weight, steroid use and non-use of biologics were identified as risk factors for inability to ambulate outdoors. CONCLUSIONS: Although the cumulative survival rate of TKA implants was as good as 96.6% in 15 years, the cumulative rate of ability to ambulate outdoors was only 48.8%. The reason for the inability to walk outdoors was thought to be mainly due to deterioration of RA, comorbidity or muscular weakness associated with aging, rather than knee dysfunction.

Regulation of osteoarthritis development by ADAM17/Tace in articular cartilage.

INTRODUCTION: A disintegrin and metalloproteinase 17 (Adam17), also known as TNFα-converting enzyme (Tace), is a membrane-anchored protein involved in shedding of TNF, IL-6 receptor, ligands of epidermal growth factor receptor (EGFR), and Notch receptor. This study aimed to examine the role of Adam17 in adult articular cartilage and osteoarthritis (OA) pathophysiology. MATERIALS AND METHODS: Adam17 expression was examined in mouse knee joints during OA development. We analyzed OA development in tamoxifen-inducible chondrocyte-specific Adam17 knockout mice of a resection of the medial meniscus and medial collateral ligament (medial) model, destabilization of the medial meniscus (DMM) model, and aging model. We analyzed downstream pathways by in vitro experiments, and further performed intra-articular administration of an Adam17 inhibitor TAPI-0 for surgically induced mouse OA. RESULTS: Adam17 expression in mouse articular cartilage was increased by OA progression. In all models, Adam17 knockout mice showed ameliorated progression of articular cartilage degradation. Adam17 knockout decreased matrix metallopeptidase 13 (Mmp13) expression in both in vivo and in vitro experiments, whereas Adam17 activation by phorbol-12-myristate-13-acetate (PMA) increased Mmp13 and decreased aggrecan in mouse primary chondrocytes. Adam17 activation enhanced release of soluble TNF and transforming growth factor alpha, a representative EGF ligand, from mouse primary chondrocytes, while it did not change release of soluble IL-6 receptor or nuclear translocation of Notch1 intercellular domain. Intra-articular administration of the Adam17 inhibitor ameliorated OA progression. CONCLUSIONS: This study demonstrates regulation of OA development by Adam17, involvement of EGFR and TNF pathways, and the possibility of Adam17 as a therapeutic target for OA.

Irreparable Large to Massive Rotator Cuff Tears With Low-Grade Fatty Degeneration of the Infraspinatus Tendon: Minimum 7-Year Follow-up of Fascia Autograft Patch Procedure and Partial Repair.

BACKGROUND: In shoulders with irreparable massive rotator cuff tears (RCTs) with high-grade fatty degeneration (Goutallier stage 3 or 4) of the supraspinatus tendon and low-grade fatty degeneration (Goutallier stage 1 or 2) of the infraspinatus tendon (ISP), arthroscopic patch grafting (PG) has been reported as superior to partial repair (PR) regarding the ISP retear rate at short-term to midterm follow-up. However, the longer term outcomes are unclear. PURPOSE: To compare clinical and structural outcomes in the PG and PR groups at a minimum of 7 years postoperatively. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We evaluated 24 patients in the PG group and 24 patients in the PR group. We primarily used the Constant score for clinical outcomes and performed magnetic resonance imaging for structural outcomes in the PG and PR groups. The risk factors for a retear of the ISP were identified by univariate and multivariate (forward stepwise selection method) logistic regression analyses. We primarily compared values at midterm follow-up (<4 years) with values at the final follow-up (minimum 7 years) for each patient. RESULTS: The mean midterm and final follow-up times for the PG group were 41.0 and 95.1 months, respectively, compared with 35.7 and 99.3 months, respectively, for the PR group. We found significant differences for the midterm and final follow-up Constant total scores in the PG and PR groups (midterm follow-up: 79.1 vs 69.9, respectively [P = .001]; final follow-up: 76.0 vs 65.3, respectively [P = .006]) and in the Constant strength scores (midterm follow-up: 14.6 vs 8.5, respectively [P < .001]; final follow-up: 13.1 vs 8.3, respectively [P = .001]). Treatment group (PR) was a significant predictor of an ISP retear in the logistic regression analysis (odds ratio, 3.545; P = .043). CONCLUSION: Patients with low-grade massive RCTs treated with PG or PR improved significantly in terms of clinical outcomes at the midterm and final follow-up time points. However, Constant scores were significantly better in the PG group at the final follow-up.

Probable Nipa Palm Wine-Associated Hepatitis A Outbreak after Attending a Funeral Ceremony in Sabah.

Foodborne outbreaks of hepatitis A virus (HAV) are most commonly associated with fresh and frozen produce and with various types of shellfish. Alcoholic beverage-borne outbreaks of hepatitis A are extremely rare. Here, we report an outbreak of hepatitis A associated with the consumption of a traditional wine at a funeral ceremony in the Sabah state of Malaysian Borneo. Confirmed cases were determined by serum anti-HAV immunoglobulin M and/or for fecal HAV by reverse transcription polymerase chain reaction (RT-PCR). The amplicons of RT-PCR were subjected to nucleotide sequencing followed by phylogenetic analysis. We conducted a 1:2 case-control study to identify the possible exposure that led to the outbreak. Sixteen patients met the case definition, they were 18 to 58 years old and 90% of them were males. The case-control study showed that the consumption of nipa palm wine during the ceremony was significantly associated (P = 0.0017) with hepatitis A infection (odds ratio, 5.44; 95% CI, 1.80-16.43). Untreated river water was used to dilute the traditional wine, which was assumed to be the source of the infection. Phylogenetically, these viruses belonged to genotype IA and formed an independent cluster with strains from Taiwan, Japan, and the Philippines. This strain might be an emerging HAV in Asian countries. Environmental assessments were performed and environmental samples were negative for HAV. The incidence of hepatitis A in Sabah was also determined and it was 0.795/100,000 population. Strict monitoring of traditional wine production should be implemented by the local authority to prevent future outbreaks.

Adipose-derived mesenchymal stem cells preserve cardiac function via ANT-1 in dilated cardiomyopathy hamster model.

INTRODUCTION: Idiopathic dilated cardiomyopathy (DCM) is associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. Mesenchymal stem cells (MSCs) can ameliorate distressed mitochondrial and structural proteins, as well as fibrosis, via the paracrine effect of cytokines. This study aimed to investigate whether the transplantation of adipose tissue-derived MSCs (ADSCs) reverses histological and functional abnormalities in the distressed myocardium of DCM-like hamsters by modulating the expression of adenine nucleotide translocase 1 (ANT-1). METHODS: Eighteen weeks after birth, ADSCs were implanted onto the cardiac surface of δ-sarcoglycan (SG)-deficient hamsters or sham surgery was performed. RESULTS: Left ventricular ejection fraction and end-systolic diameter were maintained in ADSC-treated animals for four weeks, ATP concentration was considerably elevated in the cardiomyocytes of these animals, and ANT-1 expression was significantly upregulated as well. The expression of extracellular matrix and myocardial cytoskeletal proteins, such as collagen, SG, and α-dystroglycan, did not differ between groups. However, significant improvements in myosin and Smad4 expression, cardiomyocyte hypertrophy, and capillary density occurred in the ADSC-treated group. CONCLUSIONS: We demonstrated that ADSCs might maintain cardiac function in the DCM hamster model by enhancing ATP concentration, as well as mitochondrial transporter and myosin expression, indicating their potential for DCM treatment.

Proton conductivity in mixed cation phosphate, KMg1-xH2x(PO3)·yH2O, with a layered structure at low-intermediate temperatures.

Proton solid electrolytes, which exhibit high proton conductivity at a wide range of low-intermediate temperatures (150-300 °C), are key materials for the development of fuel cells for automobiles and cogeneration systems. In this study, a benitoite-type polyphosphate, KMg1-xH2x(PO3)·yH2O, which has a non-combustible and layered structure, was investigated as a new proton conductor. The benitoite-type KMg1-xH2x(PO3)·yH2O was synthesised by a coprecipitation method. The solid solution formed in the range of x = 0-0.100 in KMg1-xH2x(PO3)3·yH2O. Multi-step weight loss due to dehydration was observed for TG/DTA measurement at 30 °C and 150 °C. We observed enhanced peaks of the vibration bands at around 1117 cm-1 and 1229 cm-1, which were attributed to the symmetric and asymmetric PO2 vibration modes, and at 743 cm-1 and 970 cm-1 due to the ns(P-O-P) and nas(P-O-P) modes as well as broad absorbance peaks at 2300 cm-1 and 2700 cm-1 corresponding to the vibration modes of ns(P-O-H) with increasing x for FTIR spectra, which suggest the introduction of protons to the crystal structure. Proton conductivity increased from x = 0 to 0.10 and then decreased at x = 0.125, where the impurity phase was observed. The sample with x = 0.10 in benitoite-type KMg1-xH2x(PO3)3·yH2O exhibited high proton conductivity of 1.4 × 10-3 S cm-1 at 150 °C and 6.5 × 10-3 S cm-1 at 250 °C under a non-humidified N2 gas flow.

A case of idiopathic myointimal hyperplasia of the mesenteric veins presenting with small bowel obstruction.

BACKGROUND: Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is a rare ischemic bowel disease with venous occlusion resulting from the proliferation of smooth muscles in the venous intima. In most patients, the disease affects rectosigmoid colon and causes persistent abdominal pain and hematochezia, which is similar to inflammatory bowel disease (IBD). In addition, it is difficult to make a precise diagnosis of IMHMV without surgery. CASE PRESENTATION: An 81-year-old woman was admitted to our hospital with mild abdominal pain, nausea and vomiting. Repeated adhesive ileus was suspected due to the previous open and laparoscopic surgeries. Surgery was planned to treat small bowel obstruction. Intraoperatively no adhesive lesions were observed. However, a mass lesion was seen at the terminal ileum, which was suspected to have caused her bowel obstruction. Partial resection of the small intestine was performed. Macroscopic and histopathological examinations of the excised specimen showed circumferential ulceration with scarring, a thickened venous wall with active inflammation, and fibrotic changes that consequently produced stenosis and obstruction of the venous lumen in the subserosa. Additionally, Elastica van Gieson staining demonstrated thickening of the venous intima. The final diagnosis was IMHMV. At two years and 8 months after the operation, the patient was well without any additional medication. CONCLUSION: IMHMV of the small intestine is rare. We described a case of IMHMV that was associated with ileus.

Ear Cartilage Reconstruction Combining Induced Pluripotent Stem Cell-Derived Cartilage and Three-Dimensional Shape-Memory Scaffold.

Microtia is a congenital malformation of the auricle. The conventional therapy for microtia is reconstruction of the auricle by using the patient's own costal cartilage. Because it is invasive to harvest costal cartilages, less invasive ways for auricular reconstruction need to be established. Recent reports have indicated a new method for the production of cartilaginous particles from human induced pluripotent stem cells. To adopt this method to create an auricular-shaped regenerative cartilage, a novel scaffold with the property of a three-dimensional shape memory was created. A scaffold with a three-dimensional shape of auricular frames composed of a helix and an antihelix, which was designed to mimic an auricular framework carved from autologous costal cartilage and transplanted in auricular reconstruction, was prepared, filled with cartilaginous particles, and subcutaneously transplanted in nude rats. The auricular-shaped regenerative cartilage maintained the given shape and cartilage features in vivo for 1 year. Our findings suggest a novel approach for auricular reconstruction.

Peritoneal adenomatoid (microcystic) mesothelioma.

There are several reports of pleural adenomatoid (microcystic) mesothelioma, but peritoneal adenomatoid mesothelioma is extremely rare. A 64-year-old Japanese woman presented with no symptoms and no asbestos exposure history. An abdominal computed tomography scan revealed multiple hypervascular masses on the liver surface, pelvic cavity and anterior peritoneum. Over 10 pieces of the multiple resected tumors showed numerous microcysts composed of a bland mesothelial cell background with rich capillary vessels. Focally, atypical cells with bizarre nuclei with prominent nucleoli were observed. Adenomatoid mesothelioma was suspected based on histochemical, immunohistochemical and fluorescence in situ hybridization findings. The tumors relapsed 4 years later and metastasized to the lung, but the patient remains alive 7 years after the first tumor resection surgery. Although the prognosis of adenomatoid mesothelioma of pleural origin is poor, the progression of this peritoneal case is slow.

[Combination Therapy of Bevacizumab plus Paclitaxel Was Effective for a Metastatic Choroidal Tumor Secondary to Breast Cancer in a Patient with Ocular Symptoms].

A 44-year-old woman experienced loss of vision and distorted vision in the right eye. After she visited our hospital, she was diagnosed with a right metastatic choroidal tumor. At the age of 35 years, she had undergone surgery for left breast cancer; as recurrence of the breast cancer was suspected, the patient was referred to our department. A CT scan revealed left axillary lymph node swelling, liver metastasis, and lung metastasis. Lymph node needle biopsy was performed under ultrasound guidance, and the pathological findings revealed recurrence of breast cancer. Combination chemotherapy of bevacizumab( BV)plus paclitaxel(PTX)was administered. After chemotherapy, the metastatic lesion had remarkably shrunk, as observed on a CT scan. Optical coherence tomography(OCT)revealed that the tumor was flattened in her right eye. Choroidal metastasis of breast cancer is rare. BV plus PTX therapy was effective for treating choroidal metastasis of breast cancer, and it should be followed by ophthalmological examination over time.