Occupational Exposure during Intraperitoneal Pressurized Aerosol Chemotherapy Using Doxorubicin in a Pig Model

Background@#This study evaluated occupational exposure levels of doxorubicin in healthcare workers performing rotational intraperitoneal pressurized aerosol chemotherapy (PIPAC) procedures. @*Methods@#All samples were collected during PIPAC procedures applying doxorubicin to an experimental animal model (pigs). All procedures were applied to seven pigs, each for approximately 44 min. Surface samples (n = 51) were obtained from substances contaminating the PIPAC devices, surrounding objects, and protective equipment. Airborne samples were also collected around the operating table (n = 39). All samples were analyzed using ultra-high performance liquid chromatography-mass spectrometry. @*Results@#Among the surface samples, doxorubicin was detected in only five samples (9.8%) that were directly exposed to antineoplastic drug aerosols in the abdominal cavity originating from PIPAC devices. The telescopes showed concentrations of 0.48–5.44 ng/cm2 and the trocar showed 0.98 ng/cm2 in the region where the spraying nozzles were inserted. The syringe line connector showed a maximum concentration of 181.07 ng/cm2, following a leakage. Contamination was not detected on the surgeons' gloves or shoes. Objects surrounding the operating table, including tables, operating lights, entrance doors, and trocar holders, were found to be uncontaminated. All air samples collected at locations where healthcare workers performed procedures were found to be uncontaminated. @*Conclusions@#Most air and surface samples were uncontaminated or showed very low doxorubicin concentrations during PIPAC procedures. However, there remains a potential for leakage, in which case dermal exposure may occur. Safety protocols related to leakage accidents, selection of appropriate protective equipment, and the use of disposable devices are necessary to prevent occupational exposure.

Association Between Gait and Dysautonomia in Patients With De Novo Parkinson’s Disease: Forward Gait Versus Backward Gait

Objective@#Studies on gait and autonomic dysfunction have been insufficient so far, particularly de novo Parkinson’s disease (PD). The aim of this study was to identify the association between gait dynamics and autonomic dysfunction in patients with de novo PD. @*Methods@#A total 38 patients with de novo PD were retrospectively included in this study. Details of patients’ dysautonomia were assessed using the Scales for Outcomes in Parkinson’s Disease-Autonomic Dysfunction (SCOPA-AUT). For assessment of gait, a computerized gait analysis was performed using the GAITRite system for forward gait and backward gait. High SCOPA-AUT score (PD-HSAS) group and low SCOPA-AUT score (PD-LSAS) group were identified according to their SCOPA-AUT scores. @*Results@#Nineteen (50%) patients with high SCOPA-AUT scores above median value (12.5) were assigned into the PD-HSAS group and others were assigned to the PD-LSAS group. Compared with the PD-LSAS group, the PD-HSAS group exhibited slower gait, shorter stride, decreased cadence, increased double support phase, decreased swing phase, and increased variability in swing time. Total SCOPA-AUT score showed significantly positive correlations with gait variability and instability but a negative correlation with gait hypokinesia. In subdomain analysis, urinary dysautonomia was highly associated with impairment of gait dynamics. All significant results were found to be more remarkable in backward gait than in forward gait. @*Conclusion@#Our findings suggest that alteration in gait dynamics, especially backward gait, is highly associated with autonomic dysfunction in patients with de novo PD.

Rotational intraperitoneal pressurized aerosol chemotherapy with paclitaxel and cisplatin: pharmacokinetics, tissue concentrations, and toxicities in a pig model / 부인종양

Objective@#We used paclitaxel and cisplatin, known to be effective in intraperitoneal chemotherapy, in a novel prototype of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) and evaluated the pharmacokinetics, tissue concentrations, and toxicities in a pig model. @*Methods@#We developed RIPAC, including the nozzle with the conical pendulum motion, and used 10% of intravenous doses of paclitaxel and cisplatin. We used high-performance liquid chromatography followed by tandem mass spectrometry to analyze serum and tissue concentrations. We applied a non-compartment model to study pharmacokinetics to analyze the time-dependent serum concentrations measured before RIPAC to 48 hours. We evaluated the difference in tissue concentrations between twelve peritoneal regions by the modified peritoneal cancer index. For evaluating toxicities, we observed hepatic and renal function until 4 days after RIPAC. @*Results@#Six pigs underwent RIPAC using paclitaxel (n=3) and cisplatin (n=3). The peak serum concentration (Cmax) and the area under the curve were higher for cisplatin, while the time to the peak serum concentration (Tmax) was longer for paclitaxel. Moreover, the parietal peritoneum showed higher tissue concentrations than the visceral peritoneum, and the ratio of tissue to serum concentrations using Cmax was higher for paclitaxel (172.2–6,237.9) than for cisplatin (0.1–9.3). However, there were no renal and hepatic toxicities after RIPAC with paclitaxel or cisplatin. @*Conclusion@#Delayed absorption of paclitaxel sprayed by RIPAC into the peritoneum to the bloodstream may lead to higher tissue concentrations at different regions and lower serum concentrations than cisplatin.

Two Schwannomas Derived from the Ulnar Nerve Confirmed by Ultrasonography

Schwannoma is a rare tumor from the peripheral nerve and is mainly found alone. Diagnosis is made by ultrasonography or magnetic resonance imaging, and magnetic resonance imaging is preferred to ultrasonography for differential diagnosis of mass. After diagnosis, treatment is performed through surgical excision. In this case, a very small-sized neuropathy-causing lesion was identified through ultrasonography with electrodiagnostic study, and the other mass in the same nerve was discovered by chance through ultrasonography. Both masses were identified as schwannoma originating from the ulnar nerve and were successfully excised. We confirmed the advantages of ultrasonography in the rare diagnosis and again showed that ultrasonography has a diagnostic value that is not inferior to magnetic resonance imaging. Also, cases of multiple schwannomas confined to the ulnar nerve are rare and have been rarely reported worldwide. Therefore, it is reported together with the previous reports.

Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor

Purpose@#Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. @*Materials and Methods@#The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. @*Results@#We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. @*Conclusion@#The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

The Effects of Anti-glaucoma Eyedrops on Corneal Hysteresis in Patients with Open-angle Glaucoma and Glaucoma-suspect

Purpose@#We explored the effects of topical anti-glaucoma medications on the corneal biochemical properties of patients with open-angle glaucoma (OAG) and glaucoma suspect (GS patients). @*Methods@#We retrospectively reviewed data on 115 OAG and 98 GS patients (225 and 128 eyes respectively). Corneal hysteresis (CH) was measured using an ocular response analyzer. Factors influencing CH were determined using a generalized estimation equation. @*Results@#The mean CH was lower in OAG than GS patients (p < 0.001). A lower cornea-compensated intraocular pressure, concomitant use of a beta-adrenergic blocker and an alpha2-adrenergic agonist, a higher visual field mean deviation, and a larger central corneal thickness were associated with a higher CH in the OAG group. @*Conclusions@#Concomitant use of a topical beta-adrenergic blocker and an alpha2-adrenergic agonist was associated with a higher CH.

Association between Laterality and Location of Deep Vein Thrombosis of Lower Extremity and Pulmonary Embolism

Purpose@#The aim of this study was to investigate the relationship between the anatomical location of thrombi in the lower extremities and the development of pulmonary embolism (PE). @*Materials and Methods@#We collected and analyzed the data of patients diagnosed with deep vein thrombosis (DVT) of the lower extremities between 2006 and 2015, and included those whose computed tomography (CT) data were available for PE identification. We evaluated the relationship between the laterality and the proximal/distal location of the thrombi in lower extremites and the location of PE. @*Results@#CT images were available for 388/452 patients with DVT. After excluding 32 cases with bilateral involvement, 356 cases were included for analysis in this study. The ratio of DVT in the left:right leg was 232:124. PEs developed in 121 (52.2%) patients with left-sided DVT and in 78 (62.9%) with right-sided DVT (P=0.052). PEs in the main pulmonary arteries developed in 36 (15.5%) patients with left leg DVT and in 30 (24.2%) with right leg DVT (P=0.045). The most frequent site of thrombosis associated with the development of PE was the left iliac vein (59/199, 29.6%). According to the anatomical segment of the leg affected by DVT, patients with DVT in the right femoral vein (50/71, 70.4%; P=0.016) had the highest rate of occurrence of PE. @*Conclusion@#PE develops more frequently in patients with right-sided DVT than in those with left-sided DVT. Therefore, careful observation for the possible development of PE is recommended in cases with right-sided DVT of the lower extremity.

Vaginal delivery after robot-assisted uterine artery-preserving radical trachelectomy for early-stage cervical cancer

Radical trachelectomy is conducted in women with early stage cervical cancer who strongly desire fertility preservation. To improve fertility outcomes, the preservation of the uterine artery has been suggested, which can be feasible by minimally invasive surgery using laparoscopy or robots. Although cesarean delivery is required for maternal and fetal health, vaginal delivery is a concern due to the fast delivery process of risk of preterm labor. We report a case of a 32-year-old nulliparous woman with stage IB1 cervical cancer who underwent robot-assisted uterine artery-preserving radical trachelectomy for improving fertility. This case is meaningful because she delivered by vaginal delivery after incision of the fibrotic ring at the level of uterovaginal anastomosis because delivery proceeded too quickly prior to the preparation of the cesarean delivery.

Reproducibility and diagnostic performance of the vascular index of superb microvascular imaging in real-time breast ultrasonography for evaluating breast masses

Purpose@#This study aimed to evaluate the reproducibility and diagnostic performance of a quantitative parameter of superb microvascular imaging (SMI) in real-time breast ultrasonography (US) for differentiating benign from malignant breast masses. @*Methods@#Eighty-seven breast masses in 75 patients who underwent both B-mode US and SMI before US-guided core needle biopsy were included in this study. Two radiologists performed B-mode US and measured the vascular index (VI) of SMI respectively for each lesion in real time. Intraobserver and interobserver agreements were analyzed for the VI of SMI. The diagnostic performance of B-mode US using the Breast Imaging Reporting and Database System lexicon and combined use with the VI of SMI was evaluated compared to pathology. @*Results@#The median VI of malignant masses (n=32) was significantly higher than that of benign masses (n=55) (7.6% and 2.6%, respectively; P<0.001). The intraobserver agreement for VI was excellent regardless of the pathology, size, or depth of the lesion. The interobserver agreement for VI was excellent regardless of the presence of a measurement interval. The interobserver agreement for the final diagnostic decision was improved by combining B-mode US and VI (κ=0.883) in comparison with B-mode US only (κ=0.617). Adding VI led to significant improvements in the specificity (87.2% vs. 52.7%, 83.6% vs. 49.0%), accuracy (89.7% vs. 69.3%, 84.0% vs. 65.9%) and positive predictive value (81.5% vs. 55.1%, 75.6% vs. 52.6%) of B-mode US for both observers compared with B-mode US alone (all, P=0.001). @*Conclusion@#The VI of SMI for real-time breast US is highly reproducible and leads to improved diagnostic performance for differentiating between benign and malignant breast lesions in combination with B-mode US.

Electronic Cigarette or Vaping Product Use-Associated Lung Injury: A Case Report

Electronic cigarette (e-cigarette) or vaping product use-associated lung injury (EVALI) has emerged as a social issue as e-cigarette use is rapidly increasing worldwide and is related to many deaths in the United States. To our knowledge, this is the first case report of EVALI in South Korea of a 24-year-old man with acute respiratory symptoms and a history of e-cigarette use. Chest CT revealed diffuse bilateral ground-glass opacities with subpleural sparing, airspace consolidation, and centrilobular micronodules as typical patterns of EVALI with organizing pneumonia and diffuse alveolar damage. Infection was excluded with meticulous laboratory examinations, and the patients’ illnesses were not attributed to other causes. EVALI was diagnosed by meeting the diagnostic criteria with consistent clinico-radiologic findings through a multidisciplinary approach. Radiologists should have good knowledge of EVALI radiologic findings and play a cardinal role in the proper diagnosis and management of EVALI.

Evaluation of Reduced Port Laparoscopic Distal Gastrectomy Performed by a Novice Surgeon

Purpose@#Reduced port laparoscopic distal gastrectomy (RPLDG) using 3 ports is less invasive than conventional laparoscopic distal gastrectomy (CLDG) using 5 ports. Although RPLDG performed by expert surgeons is safe and feasible, novice surgeons have difficulty performing this procedure. This study evaluated the surgical outcomes and feasibility of RPLDG performed by a novice surgeon. @*Materials and Methods@#The records of 136 patients who underwent laparoscopic distal gastrectomy for gastric cancer performed by a single novice surgeon between May 2016 and December 2018 were retrospectively reviewed. Among these 136 patients, 52 underwent RPLDG and 84 underwent CLDG. The clinicopathological characteristics, operative outcomes, and short-term postoperative outcomes of the 2 groups were compared. @*Results@#The percentage of women was significantly higher in the RPLDG group than in the CLDG group (48.1% vs. 31%; P=0.045), but other baseline characteristics did not differ significantly between the groups. Billroth II anastomosis was performed significantly more frequent (90.4% vs. 73.8%, P=0.015) and operation time was significantly shorter (207.1±43.3 min vs. 225.5±44.6 min, P=0.020) in the RPLDG group than in the CLDG group. The time to first flatus, postoperative pain score, length of postoperative hospital stay, and incidence and severity of complications did not differ significantly between the groups. Analysis of the learning curve based on the operation time showed that performing RPLDG on 20–30 patients was required to achieve technical proficiency. @*Conclusions@#RPLDG is a safe and feasible surgical procedure for the treatment of gastric cancer, even when performed by a novice surgeon.

Transection of the Common Carotid and Vertebral Arteries Following a Penetrating Neck Injury

A case of a 30-year-old man who was admitted following a penetrating neck injury is presented. A clinical examination and operative findings identified semi-comatose mentality, neck muscle laceration, and transection of the left common carotid and vertebral arteries and the internal jugular vein. During the operation, the carotid arteries were repaired by interposition grafting, and the internal jugular vein was ligated. The vertebral artery was managed by interventional embolization. Although the patient had some neurological deficit, he was discharged on postoperative Day 52. This surgical case prompted a discussion regarding neurological outcomes, and surgical and endovascular treatment following vascular neck injury.

Parapapillary Intrachoroidal Cavitation in Glaucoma: Association with Choroidal Microvasculature Dropout

Purpose@#To characterize the choroidal microvasculature in glaucomatous eyes with parapapillary intrachoroidal cavitation (PICC) using optical coherence tomography angiography (OCTA) and its association with parapapillary choroidal microvasculature dropout (MvD). @*Methods@#This study included 47 glaucomatous eyes with PICC, as identified by color fundus photography and optical coherence tomography scanning of the optic nerve head area. Peripapillary choroidal microvasculature was evaluated on en-face OCTA images. Choroidal MvD was defined as a focal sectoral capillary dropout with no visible microvascular network. @*Results@#PICC was visible as a well-demarcated area with homogeneously reduced vessel density in en-face OCTA images of the choroidal layer. MvD was detected in 42 eyes (89.4%). Although located in the juxtapapillary area adjacent to the PICC, MvD was confined to the area of parapapillary atrophy. MvD observed in OCTA en-face images was distinguished from the area of PICC by the absence of vascular signal. Of the 50 PICCs, 49 (98.0%) had hemifield visual field defects at the location corresponding to the hemispheric location of PICC. @*Conclusions@#PICC was found to have a characteristic microvascular feature in choroidal en-face OCTA images, and to be topographically associated with glaucomatous visual field defect. PICC was frequently accompanied by MvD and was located adjacent to the area of MvD, suggesting that PICC and MvD have similar pathogenesis.

Association between Laterality and Location of Deep Vein Thrombosis of Lower Extremity and Pulmonary Embolism

Purpose@#The aim of this study was to investigate the relationship between the anatomical location of thrombi in the lower extremities and the development of pulmonary embolism (PE). @*Materials and Methods@#We collected and analyzed the data of patients diagnosed with deep vein thrombosis (DVT) of the lower extremities between 2006 and 2015, and included those whose computed tomography (CT) data were available for PE identification. We evaluated the relationship between the laterality and the proximal/distal location of the thrombi in lower extremites and the location of PE. @*Results@#CT images were available for 388/452 patients with DVT. After excluding 32 cases with bilateral involvement, 356 cases were included for analysis in this study. The ratio of DVT in the left:right leg was 232:124. PEs developed in 121 (52.2%) patients with left-sided DVT and in 78 (62.9%) with right-sided DVT (P=0.052). PEs in the main pulmonary arteries developed in 36 (15.5%) patients with left leg DVT and in 30 (24.2%) with right leg DVT (P=0.045). The most frequent site of thrombosis associated with the development of PE was the left iliac vein (59/199, 29.6%). According to the anatomical segment of the leg affected by DVT, patients with DVT in the right femoral vein (50/71, 70.4%; P=0.016) had the highest rate of occurrence of PE. @*Conclusion@#PE develops more frequently in patients with right-sided DVT than in those with left-sided DVT. Therefore, careful observation for the possible development of PE is recommended in cases with right-sided DVT of the lower extremity.

Vaginal delivery after robot-assisted uterine artery-preserving radical trachelectomy for early-stage cervical cancer

Radical trachelectomy is conducted in women with early stage cervical cancer who strongly desire fertility preservation. To improve fertility outcomes, the preservation of the uterine artery has been suggested, which can be feasible by minimally invasive surgery using laparoscopy or robots. Although cesarean delivery is required for maternal and fetal health, vaginal delivery is a concern due to the fast delivery process of risk of preterm labor. We report a case of a 32-year-old nulliparous woman with stage IB1 cervical cancer who underwent robot-assisted uterine artery-preserving radical trachelectomy for improving fertility. This case is meaningful because she delivered by vaginal delivery after incision of the fibrotic ring at the level of uterovaginal anastomosis because delivery proceeded too quickly prior to the preparation of the cesarean delivery.

High-Grade Mucoepidermoid Carcinoma Ex Metastasizing Pleomorphic Adenomas in the Parotid Gland and Parapharyngeal Space: a Case Report and Literature Review

Pleomorphic adenoma is the most common benign neoplasm of the salivary glands. Its three malignant variants include carcinoma ex pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. Among the subtypes of carcinoma ex pleomorphic adenoma, high-grade mucoepidermoid carcinoma has rarely been reported. Additionally, metastasizing pleomorphic adenoma is rare.We report the imaging findings of a high-grade mucoepidermoid carcinoma ex metastasizing pleomorphic adenoma of the parotid gland and parapharyngeal space in a 42-year-old man.

Suppression of Foxo3-Gatm by miR-132-3p Accelerates Cyst Formation by Up-Regulating ROS in Autosomal Dominant Polycystic Kidney Disease

Accumulation of reactive oxygen species (ROS) is associated with the development of various diseases. However, the molecular mechanisms underlying oxidative stress that lead to such diseases like autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Here, we observed that oxidative stress markers were increased in Pkd1 f/f :HoxB7-Cre mice. Forkhead transcription factors of the O class (FOXOs) are known key regulators of the oxidative stress response, which have been observed with the expression of FoxO3a in an ADPKD mouse model in the present study. An integrated analysis of two datasets for differentially expressed miRNA, such as miRNA sequencing analysis of Pkd1 conditional knockout mice and microarray analysis of samples from ADPKD patients, showed that miR-132-3p was a key regulator of FOXO3a in ADPKD. miR-132-3p was significantly upregulated in ADPKD which directly targeted FOXO3 in both mouse and human cell lines. Interestingly, the mitochondrial gene Gatm was downregulated in ADPKD which led to a decreased inhibition of FOXO3. Overexpression of miR-132-3p coupled with knockdown of Foxo3 and Gatm increased ROS and accelerated cyst formation in 3D culture. This study reveals a novel mechanism involving miR-132-3p, Foxo3, and Gatm that is associated with the oxidative stress that occurs during cystogenesis in ADPKD.

Mammography with a fully automated breast volumetric software as a novel method for estimating the preoperative breast volume prior to mastectomy

Purpose@#Increasing interest in maintaining a positive body image following breast cancer surgery has become an important aspect of reconstruction surgery. Volume matching of the reconstructed breast to natural breasts is the most important consideration. This study aimed to explore the feasibility of using mammography with a fully automated breast volumetric software to measure the preoperative breast volume in patients with breast cancer. @*Methods@#We evaluated patients who underwent a total mastectomy between July 2016 and February 2021. The specimen volume following total mastectomy was compared with breast volume estimates using a fully automated volumetric software (Quantra ver. 2.1.1) and 4 other previously described mammography-based prediction methods. The association between the estimates and mastectomy specimen volume was assessed using Pearson correlation and Bland-Altman analysis. @*Results@#Sixty-six patients were included. Compared with previously described mammography-based methods, Quantra estimates were more strongly correlated with mastectomy specimen volume in the entire, fatty, and dense breast groups (r = 0.920, 0.921, and 0.915, respectively; P < 0.001). In applying Quantra estimates for measuring preoperative breast volume, we adjusted a simple equation: mastectomy specimen volume = Quantra estimate × 0.8. @*Conclusion@#Mammography with a fully automated breast volumetric software can be useful for measuring preoperative breast volume in patients with breast cancer who undergo reconstruction surgery.

High-Grade Mucoepidermoid Carcinoma Ex Metastasizing Pleomorphic Adenomas in the Parotid Gland and Parapharyngeal Space: a Case Report and Literature Review

Pleomorphic adenoma is the most common benign neoplasm of the salivary glands. Its three malignant variants include carcinoma ex pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. Among the subtypes of carcinoma ex pleomorphic adenoma, high-grade mucoepidermoid carcinoma has rarely been reported. Additionally, metastasizing pleomorphic adenoma is rare.We report the imaging findings of a high-grade mucoepidermoid carcinoma ex metastasizing pleomorphic adenoma of the parotid gland and parapharyngeal space in a 42-year-old man.

Suppression of Foxo3-Gatm by miR-132-3p Accelerates Cyst Formation by Up-Regulating ROS in Autosomal Dominant Polycystic Kidney Disease

Accumulation of reactive oxygen species (ROS) is associated with the development of various diseases. However, the molecular mechanisms underlying oxidative stress that lead to such diseases like autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Here, we observed that oxidative stress markers were increased in Pkd1 f/f :HoxB7-Cre mice. Forkhead transcription factors of the O class (FOXOs) are known key regulators of the oxidative stress response, which have been observed with the expression of FoxO3a in an ADPKD mouse model in the present study. An integrated analysis of two datasets for differentially expressed miRNA, such as miRNA sequencing analysis of Pkd1 conditional knockout mice and microarray analysis of samples from ADPKD patients, showed that miR-132-3p was a key regulator of FOXO3a in ADPKD. miR-132-3p was significantly upregulated in ADPKD which directly targeted FOXO3 in both mouse and human cell lines. Interestingly, the mitochondrial gene Gatm was downregulated in ADPKD which led to a decreased inhibition of FOXO3. Overexpression of miR-132-3p coupled with knockdown of Foxo3 and Gatm increased ROS and accelerated cyst formation in 3D culture. This study reveals a novel mechanism involving miR-132-3p, Foxo3, and Gatm that is associated with the oxidative stress that occurs during cystogenesis in ADPKD.