Efficacy of an assistive guide tube for improved endoscopic access to gastrointestinal lesions: an in vivo study in a porcine model.

BACKGROUND/AIMS: Guide tube-assisted endoscopy for procedures that require repeated endoscopic access is safer and more effective than conventional endoscopy. However, its effectiveness has not been confirmed in animal studies. We assessed the usefulness of guide tube-assisted endoscopic procedures in an in vivo porcine model. METHODS: Five different guide tube-assisted endoscopic procedures were performed by experienced endoscopists on a pig weighing 32 kg. To evaluate the efficacy of these procedures, we compared the endoscopic approach time when a guide tube was used to that when it was not. Additional endoscopic procedures using a guide tube were performed, including multiple foreign body extractions, multiple polypectomies, and multiple submucosal dissections. To evaluate safety, we compared the insertion force into the proximal esophagus between the guide tube and conventional overtube methods. RESULTS: Using the endoscopic approach with a guide tube required a shorter average approach time to reach the three target lesions than when using the endoscopic approach without a guide tube (p<0.001). Compared to the conventional overtube method, the guide tube method produced a lower average resistance during insertion into the upper esophagus (p<0.001). CONCLUSION: Guide tube-assisted endoscopic procedures are effective and safe for repeated endoscopic access in an in vivo porcine model.

A narrative review of anastomotic leak in the Ivor Lewis esophagectomy: expected, accepted, but preventable.

Background and Objective: Anastomotic leak (AL) remains a common and highly morbid complication after Ivor Lewis Esophagectomy. Leak is associated with increased morbidity, mortality, strictures and even cancer recurrence. Unfortunately, despite advances in surgical technique and perioperative care, the reported frequency of AL has remained largely unchanged. Methods: A PubMed search for all English-language articles that discuss Ivor Lewis esophagectomy, AL, risk factors, and outcomes was conducted from 1901 to 2023 prioritizing research from randomized trials that evaluated outcomes from patients undergoing esophagectomy. Key Content and Findings: This narrative review will discuss the prevailing literature on AL, risk factors and outcomes with a focus on its relationship to the Ivor Lewis esophagectomy (ILE). In particular, we emphasize that the gastric conduit, as commonly created for most esophagectomy procedures, is inherently vulnerable to ischemia. We will show trends in the literature that have contributed to the high rate of postoperative complications, with a focus on the AL. In addition, we propose that the traditional Ivor Lewis procedure itself is a risk factor for AL. We review a surgical alternative that increases blood supply of the conduit, and is associated with reduced leak, no strictures, and improved surgical outcomes. Conclusions: Multiple factors contribute to AL after esophagectomy; including several current surgical practices. We believe that some of them, especially the commonly accepted approach to the gastric conduit, can be modified to optimize tissue perfusion. With further investigation, we may reduce the incidence of short and long-term anastomotic complications and improve surgical outcomes.

Discovery and Feasibility Study of Medical Fluorophore 33 as a Novel Theranostic Agent.

Fluorescent dyes have garnered significant attention as theranostic platforms owing to their inherent characteristics. In this study, we present the discovery of Medical Fluorophore 33 (MF33), a novel and potent theranostic agent with a phenaleno-isoquinolinium salt structure that can serve as a cancer therapeutic strategy. The synthesis of MF33 is readily achievable through a simple Rh(III)-catalyzed reaction. Moreover, MF33 displayed strong fluorescence signals, excellent microsomal stability, and high biocompatibility in vivo. It induces significant apoptosis in cancer cells via the p53/p21/caspase-3 signaling pathway, leading to selective cytotoxicity in various cancer cells. In vivo fluorescence imaging with MF33 enabled the visualization of sentinel lymph nodes in living mice. Notably, repeated intraperitoneal administration of MF33 resulted in antitumor activity in mice with colorectal cancer. Collectively, our findings suggest that phenaleno-isoquinolinium salt-based MF33 is a viable theranostic agent for biomedical imaging and cancer treatment.

Anti-Cancer Effect of Neural Stem Cells Transfected with Carboxylesterase and sTRAIL Genes in Animals with Brain Lesions of Lung Cancer.

A metastatic brain tumor is the most common type of malignancy in the central nervous system, which is one of the leading causes of death in patients with lung cancer. The purpose of this study is to evaluate the efficacy of a novel treatment for metastatic brain tumors with lung cancer using neural stem cells (NSCs), which encode rabbit carboxylesterase (rCE) and the secretion form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). rCE and/or sTRAIL were transduced in immortalized human fetal NSCs, HB1.F3. The cytotoxic effects of the therapeutic cells on human lung cancer cells were evaluated in vitro with the ligands and decoy receptor expression for sTRAIL in the presence of CPT-11. Human NSCs encoding rCE (F3.CE and F3.CE.sTRAIL) significantly inhibited the growth of lung cancer cells in the presence of CPT-11 in vitro. Lung cancer cells were inoculated in immune-deficient mice, and therapeutic cells were transplanted systematically through intracardiac arterial injection and then treated with CPT-11. In resting state, DR4 expression in lung cancer cells and DcR1 in NSCs increased to 70% and 90% after CPT-11 addition, respectively. The volumes of the tumors in immune-deficient mice were reduced significantly in mice with F3.CE.sTRAIL transplantation and CPT-11 treatment. The survival was also significantly prolonged with treatment with F3.sTRAIL and F3.CE plus CPT-11 as well as F3.CE.sTRAIL plus CPT-11. NSCs transduced with rCE and sTRAIL genes showed a significant anti-cancer effect on brain metastatic lung cancer in vivo and in vitro, and the effect may be synergistic when rCE/CPT-11 and sTRAIL are combined. This stem-cell-based study using two therapeutic genes of different biological effects can be translatable to clinical application.

ATF6 is a critical regulator of cadmium-mediated apoptosis in spermatocytes.

In this study, we examined the mechanisms of cadmium exposure-induced endoplasmic reticulum (ER) stress response and apoptosis in spermatocytes. Responses to cadmium toxicity were investigated using spermatocytes overexpressing p50ATF6, ATF4, and spliced XBP1s, belonging to the 3 unfolded protein response pathways. The ER stress and apoptosis response to cadmium were most strongly stimulated through the activating transcription factor 6 (ATF6) pathway; in contrast, siRNA-induced inhibition of protein expression could reduce apoptosis under stressful conditions. An in vivo experiment using mice confirmed that upregulation of p50ATF6 in the testis increased apoptosis in response to cadmium exposure. Further, when confirming the correlation between ER stress and MAPK in cadmium toxicity, p38 MAPK phosphorylation was strongly regulated by p50ATF6; p-p38 also mediated the activity of p50ATF6. Overall, these findings suggest that modulating the activity of p38 MAPK and p50ATF6 in cadmium exposure-induced toxicity can be considered a potential strategy to treat infertility.

Ondine's curse: clinical presentation with diaphragmatic pacing and spontaneous respiratory recovery. Illustrative case.

BACKGROUND: The complexity of posterior fossa surgery can often lead to rare complications due to the anatomy involved. Vestibular schwannoma resection is a common pathology in the posterior fossa, often requiring surgical intervention. Given the proximity of this space to the brainstem, cranial nerve VII/VIII complex, and posterior inferior cerebellar artery (PICA), neurovascular complications are not infrequent. A rare vascular complication from this surgical approach is a lateral medullary infarction from injury to the lateral medullary segment of the proximal PICA, leading to central hypoventilation syndrome (CHS). OBSERVATIONS: This report presents a unique case of a 51-year-old man who underwent a retrosigmoid craniectomy for resection of a vestibular schwannoma. Following surgery, the patient was unable to be weaned off the ventilator and was noted to become apneic while he slept, a clinical picture consistent with Ondine's curse. LESSONS: This report discusses the anatomical considerations of this surgical corridor leading to this complication and the management of a patient with acquired Ondine's curse and reviews the scarce literature on this uncommon cause of acquired CHS.

Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury.

The main cause of erectile dysfunction (ED) is the damage in penile cavernous endothelial cells (EC). Murine primary ECs have a limited growth potential, and the easy availability of murine ECs will facilitate the study of cavernous endothelial dysfunction in rats. This study was performed to establish immortalized rat penile cavernous ECs (rEC) and investigate how they could repair erectile dysfunction in rats with cavernous nerve injury (CNI). rEC was isolated enzymatically by collagenase digestion and were cultured. An amphotropic replication-incompetent retroviral vector encoding v-myc oncogene was used to transfect rEC for immortalization (vREC). Morphological and immunohistochemical properties of vREC were examined. Eight-week-old male Sprague-Dawley rats were divided into three groups of five rats each, including group 1 = sham operation, group 2 = bilateral CN injury, group 3 = vREC (1 × 106 cells) treatment after CNI. Erectile response was assessed at 2, 4 weeks after transplantation of vREC., Penile tissue were harvested at 4 weeks after transplantation and immune−histochemical examination was performed. vREC showed the expression of CD31, vWF, cell type-specific markers for EC by RT-PCR and flowcytometry. At 2, 4 weeks after transplantation, rats with CNI had significantly lower erectile function than control group (p < 0.05). The group transplanted with vREC showed higher erectile function than the group without vRECs (p < 0.05). vREC was established and repaired erectile dysfunction in rats with CNI. This cell line may be useful for studying mechanisms and drug screening of erectile dysfunction of rats.

Generation of induced pluripotent stem cells (cmESF-iPS-C5) derived from cynomolgus monkey ear skin fibroblasts (cmESF).

Cynomolgus monkeys, due to their close anatomical, genetic and physiological similarity to humans, have been employed as a popular laboratory non-human primate model over rodents. Primate animal induced pluripotent stem cell (iPSC) have been used to aid on the investigation of autologous regenerative therapies. Here, we reprogrammed cynomolgus monkey ear skin fibroblasts (cmESFs) into iPSCs as a starting material for autologous based study. The resulting cmESF-iPSCs with canonical features of PSCs will advance the development of autologous transplantation.

Peroxiredoxin 2 Ameliorates AßO-Mediated Autophagy by Inhibiting ROS via the ROS-NRF2-p62 Pathway in N2a-APP Swedish Cells.

In Alzheimer's disease, reactive oxygen species (ROS) are generated by the deposition of amyloid-beta oligomers (AßOs), which represent one of the important causes of neuronal cell death. Additionally, AßOs are known to induce autophagy via ROS induction. Previous studies have shown that autophagy upregulation aggravates neuronal cell death. In this study, the effects of peroxiredoxin 2 (Prx2), a member of the peroxidase family of antioxidant enzymes, on regulating AßO-mediated autophagy were investigated. Prx2 decreased AßO-mediated oxidative stress and autophagy in N2a-APPswe cells. Further, we examined the relationship between the neuronal protective effect of Prx2 and a decrease in autophagy. Similar to the effects of N-acetyl cysteine, Prx2 decreased AßO-induced ROS and inhibited p62 protein expression levels by downregulating the activation of NRF2 and its translocation to the nucleus. In addition, treatment with 3-methyladenine, an autophagy inhibitor, ameliorates neuronal cell death. Overall, these results demonstrate that the Prx2-induced decrease in autophagy was associated with the inhibition of ROS via the ROS-NRF2-p62 pathway in N2a-APPswe cells. Therefore, our results revealed that Prx2 is a potential therapeutic target in anti-Alzheimer therapy.

[Hyponatremic Seizure after Ingestion of an Oral Sulfate Tablet for Bowel Preparation for Colonoscopy].

The oral sulfate tablet (OST), commercially available as Orafang® (Pharmbio Korea Co., Seoul, Korea) in Korea, is being used increasingly because of its bowel-cleansing efficacy, safety, and tolerability in adults undergoing colonoscopy. Other bowel cleansing agents, such as polyethylene glycol and sodium picosulfate/magnesium citrate, can cause plasma volume depletion and electrolyte disturbances, such as hyponatremia. On the other hand, the OST has never been reported to cause hyponatremia in Korea. To our knowledge, the authors experienced the first case of hyponatremic seizure in an 81-year-old woman to whom an OST was administered for bowel preparation before a colonoscopy. After ingesting the OST, she presented with seizure, confusion, and dyspnea. Upon arrival, her serum sodium level was 120 mEq/L, and the urine osmolality and sodium levels were 449 mOsm/kg and 253 mOsm/kg, respectively; chest imaging suggested pulmonary edema. The associated symptoms disappeared following treatment with an intravenous injection of normal saline and 3% NaCl to normalize the sodium level. This case shows that the OST can cause hyponatremia and other severe complications related to hyponatremia.

Association between life-style, metabolic syndrome and lower urinary tract symptoms and its impact on quality of life in men ≥ 40 years.

We aimed to assess the relationship between lifestyle-related variables, metabolic syndrome, and lower urinary tract symptoms (LUTS) in men ≥ 40 years. We also assessed the impact of these variables on quality of life. From 2014 to 2020, 5355 men who underwent health check-ups with I-PSS questionnaires at our institute were included in the analysis. The impact of LUTS on sleep disorders and moderate to severe degrees of stress were assessed. Multivariate analysis was performed to determine the variables associated with LUTS and prostate volume. Moderate and severe LUTS were present in 1317 (24.6%) and 211 (3.9%) men, respectively. Moderate and severe LUTS were significantly associated with the presence of sleep disorders and stress. On multivariable analysis, age, amount of life-long smoking, marital status, income, job, and decreased HDL-cholesterol were associated with the presence of moderate to severe LUTS. Although older age and the amount of life-long smoking was associated with both voiding and storage sub-score, socioeconomic status, including marital status and income were only associated with storage sub-score. In men ≥ 40 years, stable socioeconomic status, in addition to older age, and life-long smoking amount are associated with the presence of moderate to severe LUTS, which worsens sleep quality and stress level, by worsen storage sub-score.

Osteoporosis Is Associated with an Increased Risk of Colorectal Adenoma and High-Risk Adenoma: A Retrospective, Multicenter, Cross-Sectional, Case-Control Study.

Background/Aims: The protective effects of vitamin D and calcium on colorectal neoplasms are known. Bone mineral density (BMD) may be a reliable biomarker that reflects the long-term anticancer effect of vitamin D and calcium. This study aimed to evaluate the association between BMD and colorectal adenomas including high-risk adenoma. Methods: A multicenter, cross-sectional, case-control study was conducted among participants with average risk of colorectal cancer who underwent BMD and screening colonoscopy between 2015 and 2019. The main outcome was the detection of colorectal neoplasms. The variable under consideration was low BMD (osteopenia/osteoporosis). The logistic regression model included baseline demographics, components of metabolic syndrome, fatty liver disease status, and aspirin and multivitamin use. Results: A total of 2,109 subjects were enrolled. The mean age was 52.1±10.8 years and 42.6% were male. The adenoma detection rate was 43%. Colorectal adenoma and high-risk adenoma were both more prevalent in subjects with low BMD than those with normal BMD (48.2% vs 38.8% and 12.1% vs 9.1%). In the univariate analysis, old age, male sex, smoking, metabolic components, fatty liver, and osteoporosis were significantly associated with the risk of adenoma and high-risk adenoma. In the multivariate analysis, osteoporosis was independently associated with risk of colorectal adenoma (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.11 to 2.46; p=0.014) and high-risk adenoma (OR, 1.94; 95% CI, 1.14 to 3.29; p=0.014). Conclusions: Osteoporosis is an independent risk factor of colorectal adenoma and high-risk adenoma.

Peroxiredoxin-6 regulates p38-mediated epithelial-mesenchymal transition in HCT116 colon cancer cells.

BACKGROUND: Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress induced by several factors. They regulate several signaling pathways, such as metabolism, immune response, and intracellular reactive oxygen species (ROS) homeostasis. Epithelial-mesenchymal transition (EMT) is a transforming process that induces the loss of epithelial features of cancer cells and the gain of the mesenchymal phenotype. The EMT promotes metastasis and cancer cell progression mediated by several pathways, such as mitogen-activated protein kinases (MAPKs) and epigenetic regulators. METHODS: We used Prx6 overexpressed and downregulated HCT116 cells to study the mechanism between Prx6 and colon cancer. The expression of Prx6, GAPDH, Snail, Twist1, E-cadherin, Vimentin, N-cadherin, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected by Western blotting. Additionally, an animal study for xenograft assay was conducted to explore the function of Prx6 on tumorigenesis. Cell proliferation and migration were determined by IncuCyte Cell Proliferation and colony formation assays. RESULTS: We confirmed that the expression of Prx6 and EMT signaling highly occurs in HCT116 compared with that in other colon cancer cell lines. Prx6 regulates the EMT signaling pathway by modulating EMT-related transcriptional repressors and mesenchymal genes in HCT116 colon cancer cells. Under the Prx6-overexpressed condition, HCT116 cells proliferation increased significantly. Moreover, the HCT116 cells proliferation decreased in the siPrx6-treated cells. Eleven days after HCT116 cell injection, Prx6 was overexpressed in the HCT116-injected mice, and the tumor volume increased significantly compared with that of the control mice. Furthermore, Prx6 regulates EMT signaling through p38 phosphorylation in colon cancer cells. CONCLUSION: We suggested that Prx6 regulates EMT signaling pathway through p38 phosphorylation modulation in HCT116 colon cancer cells.

Macrophage peroxiredoxin 5 deficiency promotes lung cancer progression via ROS-dependent M2-like polarization.

Strategies for cancer treatment have traditionally focused on suppressing cancer cell behavior, but many recent studies have demonstrated that regulating the tumor microenvironment (TME) can also inhibit disease progression. Macrophages are major TME components, and the direction of phenotype polarization is known to regulate tumor behavior, with M2-like polarization promoting progression. It is also known that reactive oxygen species (ROS) in macrophages drive M2 polarization, and M2 polarization promote lung cancer progression. Lung cancer patients with lower expression of the antioxidant enzyme peroxiredoxin 5 (Prx5) demonstrate poorer survival. This study revealed that Prx5 deficiency in macrophages induced M2 macrophage polarization by lung cancer. We report that injection of lung cancer cells produced larger tumors in Prx5-deficit mice than wild-type mice independent of cancer cell Prx5 expression. Through co-culture with lung cancer cell lines, Prx5-deficient macrophages exhibited M2 polarization, and reduced expression levels of the M1-associated inflammatory factors iNOS, TNFα, and Il-1ß. Moreover, these Prx5-deficient macrophages promoted the proliferation and migration of co-cultured lung cancer cells. Conversely, suppression of ROS generation by N-acetyl cysteine (NAC) inhibited the M2-like polarization of Prx5-deficient macrophages, increased expression levels of inflammatory factors, inhibited the proliferation and migration of co-cultured lung cancer cells, and suppressed tumor growth in mice. These findings suggest that blocking the M2 polarization of macrophages may promote lung cancer regression.

Physiological Functions of Thiol Peroxidases (Gpx1 and Prdx2) during Xenopus laevis Embryonic Development.

Glutathione peroxidase 1 (Gpx1) and peroxiredoxin 2 (Prdx2) belong to the thiol peroxidase family of antioxidants, and have been studied for their antioxidant functions and roles in cancers. However, the physiological significance of Gpx1 and Prdx2 during vertebrate embryogenesis are lacking. Currently, we investigated the functional roles of Gpx1 and Prdx2 during vertebrate embryogenesis using Xenopus laevis as a vertebrate model. Our investigations revealed the zygotic nature of gpx1 having its localization in the eye region of developing embryos, whereas prdx2 exhibited a maternal nature and were localized in embryonic ventral blood islands. Furthermore, the gpx1-morphants exhibited malformed eyes with incompletely detached lenses. However, the depletion of prdx2 has not established its involvement with embryogenesis. A molecular analysis of gpx1-depleted embryos revealed the perturbed expression of a cryba1-lens-specific marker and also exhibited reactive oxygen species (ROS) accumulation in the eye regions of gpx1-morphants. Additionally, transcriptomics analysis of gpx1-knockout embryos demonstrated the involvement of Wnt, cadherin, and integrin signaling pathways in the development of malformed eyes. Conclusively, our findings indicate the association of gpx1 with a complex network of embryonic developmental pathways and ROS responses, but detailed investigation is a prerequisite in order to pinpoint the mechanistic details of these interactions.

Pre-surgical assessment of mediastinal lymph node metastases in patients having ≥ 30 mm non-small-cell lung cancers.

INTRODUCTION: Computed tomography (CT) and fluorodeoxyglucose-positron-emission-tomography (FDG-PET) measurements of mediastinal lymph nodes (MLNs) of patients with non-small-cell-lung-cancers (NSCLCs) ≤ 30 mm in maximum diameter are recommended for pre-surgical prediction of MLN metastases. METHODS: We reviewed all patients at Mount Sinai Health System enrolled in the Initiative for Early Lung Cancer Research on Treatment (IELCART), prospective cohort between 2016 and 2020, who had pre-surgical FDG-PET and underwent surgery with MLN resection and/or pre-operative endobronchial ultrasound (EBUS) for a first primary NSCLC ≤ 30 mm in maximum diameter on pre-surgical CT. RESULTS: Among 470 patients, none with part-solid (n = 63) or nonsolid (n = 23) NSCLCs had MLN metastases. Solid NSCLCs were identified in 384 patients, none in typical carcinoid (n = 48) or NSCLC ≤ 10 mm in maximum diameter (n = 47, including 8 typical carcinoids) had MLN metastases. Among the remaining 297 patients with solid NSCLCs 10.1-30.0 mm, 7 (2.4%) had MLN metastases. Area-under-the-curve (AUC) for predicting MLN metastases in solid NSCLCs 10.1-30.0 mm, using the CT maximum short-axis MLN diameter was 0.62 (95% CI:0.44-0.81, p = 0.18) and using the highest SUVmax of any MLN, AUC was 0.58 (95% CI:0.39-0.78,p = 0.41). Neither AUCs were significantly different from chance alone. Optimal cutoff for prediction of MLN metastases was ≥ 18.9 mm for CT maximum short-axis diameter [sensitivity 14.3% (95%CI:0.0%-57.9%); specificity 100.0% (95%CI:98.9%-100.0%)] and for highest SUVmax was ≥ 11.7 [sensitivity 14.3% (95%CI:0.0%-57.9%) and specificity 99.7% (95%CI:98.3%-100.0%)]. CONCLUSIONS: CT and SUVmax had low sensitivity but high specificity for predicting MLN metastases in solid NSCLCs 10.1-30.0 mm. Clinical Stage IA NSCLCs ≤ 30 mm should be based on CT maximum tumor diameter and MLN maximum short-axis diameter ≤ 20 mm.

Association of obesity, visceral adiposity, and sarcopenia with an increased risk of metabolic syndrome: A retrospective study.

AIMS: Metabolic syndrome (MS) is a global health problem associated with an increased risk of diabetes mellitus (DM), cardiovascular disease (CVD), and cancer. Body composition parameters, including obesity, visceral adiposity, and sarcopenia contribute to the development of MS and CVD. Previous studies have investigated the association of individual body composition parameters with MS. Studies analyzing the association between multiple body composition parameters and MS have been rare. We aimed to investigate the association between MS and multiple body composition parameters, including obesity, visceral adiposity, and sarcopenia. METHODS: A total of 13,620 subjects who underwent voluntary routine checkups at the Health Care Center of our institution between October 2014 and December 2019 were enrolled. Only data from the first examination of subjects who underwent repeated checkups were included. Clinical and laboratory data were collected. Skeletal muscle mass and visceral fat area (VFA) were measured using bioelectrical impedance analysis. Appendicular skeletal muscle mass (ASM) was divided by body weight (in kg) and expressed as a percentage (calculated as, ASM% = ASM × 100/Weight). Data were compared between the groups based on obesity, VFA, and ASM%. Logistic regression analysis was performed to determine the risk of MS in each group. RESULTS: Body mass index and VFA were significantly higher in subjects with MS than in those without MS. ASM% was significantly lower in subjects with MS than in those without MS. Subjects with obesity, visceral adiposity, or sarcopenia had a higher prevalence of MS than those without. As the number of metabolic components increased from 0 to 5, we identified a decreasing trend of ASM% and an increasing trend of VFA and BMI (P for trend < 0.001 for all). In the paired analyses, all the three body composition parameters showed additive effects in predicting MS. In the logistic regression analysis, the three parameters were associated with an increased risk of MS after adjustment for age, sex, hypertension, DM, dyslipidemia, smoking, alcohol intake, and C-reactive protein. CONCLUSIONS: Obesity, visceral adiposity, and sarcopenia showed additive effects on MS prediction. Subjects with obesity, visceral adiposity, or sarcopenia were significantly associated with the increased risk of MS after adjustment for multiple confounders. Increasing skeletal muscle and reducing visceral fat may be strategies for the prevention or treatment of MS.

L-myc Gene Expression in Canine Fetal Fibroblasts Promotes Self-Renewal Capacity but Not Tumor Formation.

Canines are useful in mammalian preclinical studies because they are larger than rodents and share many diseases with humans. Canine fetal fibroblast cells (CFFs) are an easily accessible source of somatic cells. However, they are easily driven to senescence and become unusable with continuous in vitro culture. Therefore, to overcome these deficiencies, we investigated whether tetracycline-inducible L-myc gene expression promotes self-renewal activity and tumorigenicity in the production of induced conditional self-renewing fibroblast cells (iCSFCs). Here, we describe the characterization of a new iCSFC line immortalized by transduction with L-myc that displays in vitro self-renewal ability without tumorigenic capacity. We established conditionally inducible self-renewing fibroblast cells by transducing CFF-3 cells with L-myc under the tetracycline-inducible gene expression system. In the absence of doxycycline, the cells did not express L-myc or undergo self-renewal. The iCSFCs had a fibroblast-like morphology, normal chromosome pattern, and expressed fibroblast-specific genes and markers. However, the iCSFCs did not form tumors in a soft agar colony-forming assay. We observed higher expression of three ES modules (core pluripotency genes, polycomb repressive complex genes (PRC), and MYC-related genes) in the iCSFCs than in the CFF-3 cells; in particular, the core pluripotency genes (OCT4, SOX2, and NANOG) were markedly up-regulated compared with the PRC and MYC module genes. These results demonstrated that, in canine fetal fibroblasts, L-myc tetracycline-inducible promoter-driven gene expression induces self-renewal capacity but not tumor formation. This study suggests that L-myc gene-induced conditional self-renewing fibroblast cells can be used as an in vitro tool in a variety of biomedical studies related to drug screening.

Narrative review of anxiety and depression in patients with esophageal cancer: underappreciated and undertreated.

Depression and anxiety are emotional disorders that commonly affect patients with esophageal cancer. As a result of its high morbidity, mortality, and complication rates, this population is at particularly high risk for developing or exacerbating affective disorders; even when compared to patients with other forms of cancer. Many of the medical conditions and social behaviors that predispose patients to this disease are also independently associated with affective disorders, and likely compound their effects. Unfortunately, in the existing literature, there is wide variability in study design and diagnostic criteria. There is no standard method of evaluation, many studies are limited to written surveys, and widespread mental health screening is not included as a part of routine care. As a result, the prevalence of these illnesses remains elusive. Additionally, psychiatric and psychosocial illness can affect compliance with surveillance and treatment, and gaps in knowledge may ultimately influence patient outcomes and survival. This review will discuss the existing literature on depression and anxiety in patients with esophageal cancer. It will highlight current methods of psychological evaluation, the prevalence of affective disorders in this population, and their effects on treatment, compliance, and outcomes. It will also discuss possible screening tools, treatments and interventions for these comorbid illnesses that may improve oncologic outcomes as well as quality of life.

Investigation of droplets released during digestive endoscopy using a high-speed camera (with video): a pilot study.

BACKGROUND: A large release of droplets is often expected around the periphery of the digestive endoscope insertion site. Therefore, a sense of alarm over infection because of droplets that may be released during digestive endoscopy examination is increasing. This study aimed to investigate the droplets released during digestive endoscopy using a high-speed camera. METHODS: We utilized a high-speed camera (FASTCAM SA-3, Photron Limited) capable of recording small, transparent droplets with a black background and high-brightness lighting. The obtained video files were analyzed using post-processing software. We divided the 20 models into the control (a spray bottle model and a cough model) and experimental groups (digestive endoscopy models). The sedative, proficiency of digestive endoscopy and the amount of gas injected were modulated to change the level of released droplets. RESULTS: For the control groups, droplets were clearly observed using a high-speed camera. However, no droplet larger than 10 µm in size was observed in the experimental groups. Furthermore, the changes in the sedative, proficiency of digestive endoscopy, and amount of gas injected did not affect droplet formation. CONCLUSIONS: Based on high-speed camera photography, the risk of droplet generation during digestive endoscopy was not higher than that during violent expiratory events, such as coughing and sneezing.