Risk of tuberculosis after endoscopic resection and gastrectomy in gastric cancer: nationwide population-based matched cohort study.

BACKGROUND: This study aimed to investigate the association between gastrectomy and endoscopic resection for gastric cancer and the subsequent tuberculosis incidence. METHODS: We conducted a nationwide matched cohort study using data from the Korea National Health Insurance Service from 2013 to 2019. We created two cohorts: patients who underwent gastrectomy and those who had endoscopic resection. Each patient was matched 1:1 with an unexposed individual based on index year, age, sex, income, and various comorbidities. The primary outcome was the incidence of tuberculosis during the follow-up period. RESULTS: Our study comprised 90,886 gastrectomy patients and 46,759 endoscopic resection patients. The tuberculosis incidence was significantly higher in the gastrectomy group compared to its matched non-gastrectomy group (IRR 1.69, 95% CI 1.43-1.99, p < .001). In contrast, there was no significant difference in tuberculosis incidence between the endoscopic resection group and its matched non-resection group (IRR 0.95, 95% CI 0.75-1.19, p = 0.627). The Kaplan-Meier cumulative incidence also did not differ between the two groups. However, tuberculosis incidence significantly increased in the first year after endoscopic resection. CONCLUSION: Gastrectomy for gastric cancer is associated with a higher incidence of subsequent tuberculosis, while no significant association was observed for endoscopic resection. However, tuberculosis incidence increases significantly during the first year after endoscopic resection.

Lymphangioleiomyomatosis and mTOR inhibitors in real world-a narrative review.

Background and Objective: Lymphangioleiomyomatosis (LAM) is a rare disease developing mostly on lung and leading to various pulmonary and extra-pulmonary manifestations. Management of this intractable illness has been mostly symptomatic and supplementary until the advent and application of a novel drug, i.e., the mechanistic target of rapamycin (mTOR) inhibitor, and successful disease control using mTOR inhibitors is improving LAM patients. Although mTOR inhibitors are showing remarkable results there are still many rooms for further progress, and partly solved issues on problems seen in LAM still remain. We searched multiple reports and investigational studies regarding LAM, especially the therapeutic achievement won by mTOR inhibitors. This article summarized several characteristics of LAM including pathogenesis, clinical manifestation, laboratory findings, and management. We also attempted to review the latest knowledge and efficacy of mTOR inhibitors and some new drugs. Methods: Online searching of literature was performed. The National Center for Biotechnology Information (NCBI), PubMed, Cochrane Library, Google Scholar, and EMBASE were searched. Key Content and Findings: LAM is a genetic disease with a high predilection toward female subjects. Not only lung but also other organs are involved, hence extrapulmonary symptoms and signs are also noted. Representative objective finding is a progressive deterioration of lung function, sometimes leading to respiratory failure. Supportive and symptomatic care has been the mainstay of therapy with suboptimal result, until a novel drug, the mTOR inhibitor, was developed. Successful deterrence of disease progression was achieved on management with mTOR inhibitors. Several unsolved problems using mTOR inhibitors are a pending issue, such as duration of treatment. Conclusions: LAM has been a rare, stubborn disease to ameliorate in health due to its complex pathogenesis and accompanied by other manifestations. Adopting various tools for relief has been usually suboptimal, but mTOR inhibitors proved to achieve significant improvement in various aspects. Further investigation is needed including refinement of currently available therapeutic applications, development of novel remedies, and so on.

KPT6566 induces apoptotic cell death and suppresses the tumorigenicity of testicular germ cell tumors.

Testicular germ cell tumors (TGCTs) frequently affect adolescent and young adult males. Although TGCT is more responsive to cisplatin-based chemotherapy than other solid tumors, some patients are nonresponders, and following treatment, many patients continue to experience acute and long-term cytotoxic effects from cisplatin-based chemotherapy. Consequently, it is imperative to develop new therapeutic modalities for treatment-resistant TGCTs. Peptidyl-prolyl isomerase (Pin1) regulates the activity and stability of many cancer-associated target proteins. Prior findings suggest that Pin1 contributes to the pathogenesis of multiple human cancers. However, the specific function of Pin1 in TGCTs has not yet been elucidated. TGCT cell proliferation and viability were examined using cell cycle analysis and apoptosis assays following treatment with KPT6566, a potent, selective Pin1 inhibitor that covalently binds to the catalytic domain of Pin1. A xenograft mouse model was used to assess the effect of KPT6566 on tumor growth in vivo. KPT6566 effectively suppressed cell proliferation, colony formation, and ATP production in P19 and NCCIT cells. Further, KPT6566 induced apoptotic cell death by generating cellular reactive oxygen species and downregulating the embryonic transcription factors Oct-4 and Sox2. Finally, KPT6566 treatment significantly reduced tumor volume and mass in P19 cell xenografts. The Pin1 inhibitor KPT6566 has significant antiproliferative and antitumor effects in TGCT cells. These findings suggest that Pin1 inhibitors could be considered as a potential therapeutic approach for TGCTs.

Optimal Nozzle Position and Patient's Posture to Enhance Drug Delivery into the Peritoneum during Rotational Intraperitoneal Pressurized Aerosol Chemotherapy in a Swine Model.

Even though rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) has been developed to improve the distribution and penetration depth of anti-cancer agents by pressurized intraperitoneal aerosol chemotherapy (PIPAC), the optimal nozzle position and patient's posture have not been investigated. Thus, we used nine pigs weighing 50-60 kg, and sprayed 150 mL of 1% methylene blue as an aerosol through the nozzle, DreamPen® (Dreampac Corp., Wonju, Republic of Korea), with a flow rate of 0.6 ml/min under a pressure of 140 to 150 psi for RIPAC in six and three pigs with supine and Trendelenburg positions, respectively. When we evaluated its distribution and penetration depth, even distribution among 13 regions of the abdomen was observed in three pigs with Trendelenburg position regardless of the depth of the nozzle. Regarding penetration depth, the numbers of regions with maximal penetration depth were high in the 2 cm depth of the nozzle with supine position (n = 5) and the 4 cm depth with Trendelenburg position (n = 3). Conclusively, even distribution and maximal penetration of anti-cancer agents can be expected during RIPAC in the medium depth (4 cm) between the nozzle inlet and the visceral peritoneum located on the opposite side of it and the Trendelenburg position.

Triazole-Bridged Zinc Dinuclear Complexes: Mechanochemical Synthesis, Crystal Structure, and Biological Activity.

Two zinc (Zn) complexes, [Zn2(DAT)2Cl4] (I) and [Zn2(DAT)2(NO3)4] (II), were prepared by grinding 3,5-diamino-1,2,4-triazole (C2H5N5, DAT) with Zn precursors such as ZnCl2 and Zn(NO3)2, respectively. This solid-state reaction gives the corresponding Zn complex as the sole product in over 99% yield. This mechanochemical method promotes the selective formation of Zn complexes different from those obtained using the conventional solution-based route. The crystal structures of the two complexes were analyzed by single-crystal X-ray diffraction. Complex (I) crystallizes in the monoclinic space group P21/c, whereas complex (II) crystallizes in the triclinic space group P 1̅. Each complex is characterized by the presence of a characteristic DAT-bridged dimer with one DAT ligand per Zn atom, and the DAT ligand provides a bridge between the two Zn metals. All Zn centers of (I) and (II) adopted a slightly distorted tetrahedral geometry. Both complexes contain a hexanuclear Zn2N4 ring, but their ring structures are different. Complex (I) possesses a boat geometry, while complex (II) has a nearly planar structure. The Zn-bound chlorides of complex (I) form intermolecular N-H···Cl hydrogen bonds that link neighboring molecules. In complex (II), the O atoms in the nitrate groups are hydrogen-bonded to the DAT ligand via O···H-N linkages. Both complexes exhibit blue emissions in the solid state at ambient temperature. They were evaluated as anticancer agents in HeLa, NCCIT, and MCF-7 cancer cell lines, exhibiting promising anticancer activities.

Histopathological Features of Myxoid Pleomorphic Liposarcoma in an African Pygmy Hedgehog (Atelerix Albiventris).

Myxoid pleomorphic liposarcoma is characterized by pathological features of both pleomorphic liposarcoma and myxoid liposarcoma, as the name suggests. In this case, a myxoid pleomorphic liposarcoma was observed in a 5-year-old male African pygmy hedgehog. It consisted of ~60% of the myxoid substance area with proliferating round cells and ~30% of pleomorphic neoplastic cells. The subject presented with extrapulmonary metastasis, but a good prognosis during 6 months of follow-up, which is similar to the characteristics of myxoid liposarcoma. The histopathological features of myxoid pleomorphic liposarcoma may reflect the features of either myxoid liposarcoma or pleomorphic liposarcoma depending on the proportion of each histopathological feature. The proportion of the pleomorphic area and the myxoid area may offer information on the prognosis and metastasis of myxoid pleomorphic liposarcoma, which will be helpful for setting up a treatment plan. Thus, analyzing the proportion of pleomorphic area and myxoid area could be suggested as one of the ways to predict clinical outcomes. In addition to the fact that this is the first case of a myxoid pleomorphic liposarcoma in hedgehogs, this case is meaningful, considering the unique histopathological characteristics and rare incidence of myxoid pleomorphic liposarcoma that could be important in humans as well.

Long-term treatment of allogeneic adipose-derived stem cells in a dog with rheumatoid arthritis.

BACKGROUND: Although there are growing demands for stem cell-based therapy for companion animals in various diseases, a few clinical trials have been reported. Moreover, most of them are the results from only one or a few times of stem cell injection. OBJECTIVES: The aim of this study is to describe a long-term treatment with allogeneic adipose-derived stem cells (ASCs) in a dog with rheumatoid arthritis (RA), which is a rare canine disease. METHODS: The dog with RA received intravascular injection of allogeneic ASCs derived from two healthy donors once a month for 11 months. To assess therapeutic effects of ASCs, orthopedic examination and clinical evaluation was performed. Cytokines of tumor necrosis factor-α and interleukin-6 in the plasma were measured using ELISA analysis. RESULTS: Despite this repeated and long-term administration of allogeneic ASCs, there were no side effects such as immunorejection responses or cell toxicity. The orthopedic examination score for the dog decreased after ASCs treatment, and the clinical condition of the dog and owner's satisfaction were very good. CONCLUSIONS: Although ASCs has been suggested as one of the options for RA treatment because of its anti-inflammatory and immunosuppressive functions, it has never been used to treat RA in dogs. The present report describes a case of canine RA treated with allogeneic ASCs for long-term in which the dog showed clinical improvement without adverse effects.

[Development of a Diabetic Foot Ulceration Prediction Model and Nomogram].

PURPOSE: This study aimed to identify the risk factors for diabetic foot ulceration (DFU) to develop and evaluate the performance of a DFU prediction model and nomogram among people with diabetes mellitus (DM). METHODS: This unmatched case-control study was conducted with 379 adult patients (118 patients with DM and 261 controls) from four general hospitals in South Korea. Data were collected through a structured questionnaire, foot examination, and review of patients' electronic health records. Multiple logistic regression analysis was performed to build the DFU prediction model and nomogram. Further, their performance was analyzed using the Lemeshow-Hosmer test, concordance statistic (C-statistic), and sensitivity/specificity analyses in training and test samples. RESULTS: The prediction model was based on risk factors including previous foot ulcer or amputation, peripheral vascular disease, peripheral neuropathy, current smoking, and chronic kidney disease. The calibration of the DFU nomogram was appropriate (χ² = 5.85, p = .321). The C-statistic of the DFU nomogram was .95 (95% confidence interval .93~.97) for both the training and test samples. For clinical usefulness, the sensitivity and specificity obtained were 88.5% and 85.7%, respectively at 110 points in the training sample. The performance of the nomogram was better in male patients or those having DM for more than 10 years. CONCLUSION: The nomogram of the DFU prediction model shows good performance, and is thereby recommended for monitoring the risk of DFU and preventing the occurrence of DFU in people with DM.

Influence of Age on Skeletal Muscle Hypertrophy and Atrophy Signaling: Established Paradigms and Unexpected Links.

Skeletal muscle atrophy in an inevitable occurrence with advancing age, and a consequence of disease including cancer. Muscle atrophy in the elderly is managed by a regimen of resistance exercise and increased protein intake. Understanding the signaling that regulates muscle mass may identify potential therapeutic targets for the prevention and reversal of muscle atrophy in metabolic and neuromuscular diseases. This review covers the major anabolic and catabolic pathways that regulate skeletal muscle mass, with a focus on recent progress and potential new players.

Data resource profile: the allergic disease database of the Korean National Health Insurance Service.

Researchers have been interested in probing how the environmental factors associated with allergic diseases affect the use of medical services. Considering this demand, we have constructed a database, named the Allergic Disease Database, based on the National Health Insurance Database (NHID). The NHID contains information on demographic and medical service utilization for approximately 99% of the Korean population. This study targeted 3 major allergic diseases, including allergic rhinitis, atopic dermatitis, and asthma. For the target diseases, our database provides daily medical service information, including the number of daily visits from 2013 and 2017, categorized by patients' characteristics such as address, sex, age, and duration of residence. We provide additional information, including yearly population, a number of patients, and averaged geocoding coordinates by eup, myeon, and dong district code (the smallest-scale administrative units in Korea). This information enables researchers to analyze how daily changes in the environmental factors of allergic diseases (e.g., particulate matter, sulfur dioxide, and ozone) in certain regions would influence patients' behavioral patterns of medical service utilization. Moreover, researchers can analyze long-term trends in allergic diseases and the health effects caused by environmental factors such as daily climate and pollution data. The advantages of this database are easy access to data, additional levels of geographic detail, time-efficient data-refining and processing, and a de-identification process that minimizes the exposure of identifiable personal information. All datasets included in the Allergic Disease Database can be downloaded by accessing the National Health Insurance Service data sharing webpage (https://nhiss.nhis.or.kr).

Mesenchymal Stem Cell and MicroRNA Therapy of Musculoskeletal Diseases.

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

Longitudinal Changes in Clinical Features, Management, and Outcomes of Idiopathic Pulmonary Fibrosis. A Nationwide Cohort Study.

Rationale: In recent decades, diagnosis and treatment recommendations for idiopathic pulmonary fibrosis (IPF) have changed. In Korea, the average life expectancy has increased, unmet healthcare needs have been reduced, and the number of computed tomographic examinations performed has nearly doubled. The Korean Interstitial Lung Disease Study Group conducted a nationwide cohort study for idiopathic interstitial pneumonia, including IPF, and established a registry for IPF.Objectives: Using study data collected by the study group, this study aimed to evaluate longitudinal changes in clinical features, diagnosis, treatment, and mortality and analyze the extent to which changes in medication usage affected IPF-associated mortality.Methods: The study population included newly diagnosed patients with IPF from a cohort study (January 2002 to September 2008, n = 1,839, 2008 group) and prospective registry (January 2012 to August 2018, n = 1,345, 2018 group). Survival curves were estimated using the Kaplan-Meier method, and Cox regression models were used to identify mortality-associated risk factors in each group.Results: The 2018 group was younger, had fewer symptoms, had less honeycombing, underwent more serologic autoimmune marker and pulmonary function tests, had higher oxygen partial pressure and lower carbon dioxide partial pressure values, was less frequently diagnosed by surgical biopsy, and had better survival than the 2008 group. Steroid use and conservative care declined, whereas N-acetylcysteine use increased in this group. Antifibrotic agents were used in only the 2018 group. In the 2008 group, N-acetylcysteine was associated with lower mortality, whereas conservative care was associated with higher mortality. In the 2018 group, the use of antifibrotic agents was associated with lower mortality, and steroid use was associated with higher mortality. The survival rates in the 2008 and 2018 non-antifibrotic agent subgroups were similar.Conclusions: This study analyzed national IPF cohort data spanning 17 years. In clinical practice, the IPF diagnosis was made earlier, steroid and immunosuppressive agent use was reduced, and antifibrotic agents were administered. The survival of patients with IPF has improved over the decades, and antifibrotic use was consistently associated with improved survival.Clinical trial registered with clinicaltrials.gov (NCT04160715).

A new type of oculocutaneous albinism with a novel OCA2 mutation.

Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders, characterized by hypopigmentation of the eyes, skin, and hair, which result in ocular abnormalities and a risk of developing skin cancer. Currently, there is no ophthalmologic procedure or drug that prevents the clinical features of OCA. Here, we report a new type of OCA in two, unrelated Korean families with the same OCA2 mutation. Affected individuals in this study are different from those of previous reports in two aspects: an inheritance pattern and clinical presentation. All reported patients with OCA have shown an autosomal recessive inheritance pattern, while our patients showed an autosomal dominant inheritance pattern. Small amounts of pigment can be acquired with age in OCA, but there is no substantial variation from adolescence to adulthood in this regard. A case where the patient attained normal pigmentation levels has never been reported. However, our patients displayed completely normal pigmentation in their late twenties. Whole exome sequencing and in-silico analysis revealed a novel mutation, OCA2 c.2338G>A p.(G780S) (NM_000275) with a high likelihood of pathogenicity. Sanger sequencing of p.G780S identified the same mutation in the affected individuals, which was not found in the family members with normal phenotype. We hypothesize that OCA2 G780S not only acts as a pathogenic variant of OCA but also induces pigmentation by enhancing the melanogenesis gene expression of other modifier genes, such as SLC45A2 and TPC2. These findings may provide further understanding of melanin biosynthesis and new treatment methods for OCA.

ATP-Dependent Chromatin Remodeler CHD9 Controls the Proliferation of Embryonic Stem Cells in a Cell Culture Condition-Dependent Manner.

Emerging evidence suggests that chromodomain-helicase-DNA-binding (CHD) proteins are involved in stem cell maintenance and differentiation via the coordination of chromatin structure and gene expression. However, the molecular function of some CHD proteins in stem cell regulation is still poorly understood. Herein, we show that Chd9 knockdown (KD) in mouse embryonic stem cells (ESCs) cultured in normal serum media, not in 2i-leukemia inhibitory factor (LIF) media, causes rapid cell proliferation. This is caused by transcriptional regulation related to the cell cycle and the response to growth factors. Our analysis showed that, unlike the serum cultured-Chd9 KD ESCs, the 2i-LIF-cultured-Chd9 KO ESCs displayed elevated levels of critical G1 phase regulators such as p21 and p27. Consistently, the DNA binding sites of CHD9 overlap with some transcription factor DNA motifs that are associated with genes regulating the cell cycle and growth pathways. These transcription factors include the cycle gene homology region (CHR), Arid5a, and LIN54. Collectively, our results provide new insights into CHD9-mediated gene transcription for controlling the cell cycle of ESCs.

Successful Treatment of a Korean Infant with Giant Cell Hepatitis with Autoimmune Hemolytic Anemia Using Rituximab.

Giant cell hepatitis with autoimmune hemolytic anemia (AHA) is a rare disease of infancy characterized by the presence of both Coombs-positive hemolytic anemia and progressive liver disease with giant cell transformation of hepatocytes. Here, we report a case involving a seven-month-old male infant who presented with AHA followed by cholestatic hepatitis. The clinical features included jaundice, pallor, and red urine. Physical examination showed generalized icterus and splenomegaly. The laboratory findings suggested warm-type AHA with cholestatic hepatitis. Liver biopsy revealed giant cell transformation of hepatocytes and moderate lobular inflammation. The patient was successfully treated with four doses of rituximab. Early relapse of hemolytic anemia and hepatitis was observed, which prompted the use of an additional salvage dose of rituximab. He is currently in clinical remission.

Mesenchymal stem cells reduce ER stress via PERK-Nrf2 pathway in an aged mouse model.

BACKGROUND AND OBJECTIVE: Mesenchymal stem cells (MSC) have been shown to ameliorate the deleterious effects of bleomycin in murine models. However, the mechanism responsible for protection from pulmonary fibrosis by stem cell therapy is still poorly understood, especially in terms of endoplasmic reticulum (ER) stress. We hypothesized that during bleomycin-induced lung injury, markers of ER stress, specifically the activation of the unfolded protein response (UPR), increase during injury, resembling the kinetics of collagen deposition in the lung described for the bleomycin model. We aimed to elucidate the possible role of MSC in ER stress modulation. METHODS: To determine the kinetics of ER stress in aged mice, the expression of ER stress markers after bleomycin lung injury was measured in old mice at different time points (days 0, 3, 7, 14 and 21). To evaluate the consequences of systemic delivery of MSC on lung ER stress in the bleomycin model, we evaluated changes in body weight, lung histology and protein expression of ER stress markers. RESULTS: The level of expression of UPR transcription factor XBP-1 and its regulator BiP was elevated at day 7 and progressively increased up to day 21. MSC inhibited BiP expression in bleomycin-induced ER stress, attenuating ER stress via the protein kinase RNA-like ER kinase (PERK)-Nrf2 pathway. The expression levels of other ER stress markers were not perturbed by MSC. CONCLUSION: Our data suggest that MSC operate on ER stress via several pathways, but the PERK-Nrf2 pathway revealed to be the main functioning pathway in our bleomycin model.

Rescue Extracorporeal Bypass to Prevent Atrioesophageal Fistula-related Air Embolism.

Atrioesophageal fistula (AEF) is a rare but disastrous complication encountered after radiofrequency catheter ablation for atrial fibrillation or flutter. Furthermore cerebral air embolism due to AEF is considered a strong predictor of mortality. In our case a patient presented with AEF and cerebral air embolism. As a rescue effort ventricular fibrillation was induced and sustained under venoarterial extracorporeal membrane oxygenation support until emergency AEF repair was feasible. Herein we report the successful use of the above measures to prevent further air embolism in a patient with radiofrequency catheter ablation-related AEF.

Effective Preparation Method of Phosphopeptides from Phosvitin and the Analysis of Peptide Profiles Using Tandem Mass Spectrometry.

The effect of high-temperature and mild-pressure (HTMP) pretreatment on the enzymatic hydrolysis of phosvitin and the structural characteristics of the phosphopeptides produced were analyzed using tandem mass spectrometry. The HTMP pretreatment hydrolyzed phosvitin at random sites and helped the subsequent enzyme hydrolysis of the peptides produced. With the HTMP pretreatment alone, 154 peptides were produced, while the use of trypsin, Protex 6L, and Multifect 14L in combination with the pretreatment produced 252, 280, and 164 peptides, respectively. The use of two enzyme combinations (trypsin + Protex 6L and trypsin + Multifect 14L) helped the hydrolysis further. The number of phosphopeptides produced increased when the modifications within the same amino acid sequences were considered. This study indicated that HTMP pretreatment was a breakthrough method to improve the enzymatic hydrolysis of phosvitin that enabled an easy production of phosvitin phosphopeptides for their subsequent functional characterizations.

No more helper adenovirus: production of gutless adenovirus (GLAd) free of adenovirus and replication-competent adenovirus (RCA) contaminants.

Gene therapy is emerging as an effective treatment option for various inherited genetic diseases. Gutless adenovirus (GLAd), also known as helper-dependent adenovirus (HDAd), has many notable characteristics as a gene delivery vector for this particular type of gene therapy, including broad tropism, high infectivity, a large transgene cargo capacity, and an absence of integration into the host genome. Additionally, GLAd ensures long-term transgene expression in host organisms owing to its minimal immunogenicity, since it was constructed following the deletion of all the genes from an adenovirus. However, the clinical use of GLAd for the treatment of inherited genetic diseases has been hampered by unavoidable contamination of the highly immunogenic adenovirus used as a helper for GLAd production. Here, we report the production of GLAd in the absence of a helper adenovirus, which was achieved with a helper plasmid instead. Utilizing this helper plasmid, we successfully produced large quantities of recombinant GLAd. Importantly, our helper plasmid-based system exclusively produced recombinant GLAd with no generation of helper plasmid-originating adenovirus and replication-competent adenovirus (RCA). The recombinant GLAd that was produced efficiently delivered transgenes regardless of their size and exhibited therapeutic potential for Huntington's disease (HD) and Duchenne muscular dystrophy (DMD). Our data indicate that our helper plasmid-based GLAd production system could become a new platform for GLAd-based gene therapy.

Sertoli Cell Tumor (SCT) in a Captive Black Bear (Ursus americanus).

A black bear of 29-year-old (Ursus americanus) died unexpectedly in captivity without any gross lesions or clinical signs. We identified a firm, lobulated, yellowish tan, and well-circumscribed mass embedded inside the testicular tissue at the time of necropsy. The tumor sections exhibited soft necrotic and hemorrhagic areas beneath its capsule. Histologically, the tumor comprised Sertoli cells arranged in tubules and solid sheets supported by prominent fibrous connective tissues. The Sertoli cells were positive for vimentin and ER-ß expression, whereas it showed negative staining for inhibin-α, cytokeratin 19, and S-100. To the best of our knowledge, this is the rare case report of testicular Sertoli cell tumor in black bear.