Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.

Purpose: The number of patients presenting with vaccination-related cardiovascular symptoms after receiving mRNA vaccines (mRNA-VRCS) is increasing. We investigated the incidence of vaccine-related adverse events (VAEs), including myocarditis and pericarditis, in patients with mRNA-VRCS after receiving BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna vaccines. Materials and Methods: We retrospectively collected data on patients presenting with mRNA-VRCS who visited the outpatient clinic of two tertiary medical centers. Clinical characteristics, laboratory findings, echocardiographic findings, and electrocardiographic findings were evaluated. VAE was defined as myocarditis or pericarditis in patients after mRNA vaccination. Clinical outcomes during short-term follow-up, including emergency room (ER) visit, hospitalization, or death, were also assessed among the patients. Results: A total of 952 patients presenting with mRNA-VRCS were included in this study, with 89.7% receiving Pfizer-BioNTech and 10.3% receiving Moderna vaccines. The mean duration from vaccination to symptom was 5.6±7.5 days. VAEs, including acute myocarditis and acute pericarditis, were confirmed in 11 (1.2%) and 10 (1.1%) patients, respectively. The VAE group showed higher rates of dyspnea, echocardiography changes, and ST-T segment changes. During the short-term follow-up period of 3 months, the VAE group showed a higher hospitalization rate compared to the control group; there was no significant difference in ER visit (p=0.320) or mortality rates (p>0.999). Conclusion Amongst the patients who experienced mRNA-VRCS, the total incidence of VAEs, including acute myocarditis and pericarditis, was 2.2%. Patients with VAEs showed higher rates of dyspnea, echocardiographic changes, and ST-T segment changes compared to those without VAEs. With or without the cardiovascular events, the prognosis in patients with mRNA-VRCS was favorable.

Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.

Purpose: The number of patients presenting with vaccination-related cardiovascular symptoms after receiving mRNA vaccines (mRNA-VRCS) is increasing. We investigated the incidence of vaccine-related adverse events (VAEs), including myocarditis and pericarditis, in patients with mRNA-VRCS after receiving BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna vaccines. Materials and Methods: We retrospectively collected data on patients presenting with mRNA-VRCS who visited the outpatient clinic of two tertiary medical centers. Clinical characteristics, laboratory findings, echocardiographic findings, and electrocardiographic findings were evaluated. VAE was defined as myocarditis or pericarditis in patients after mRNA vaccination. Clinical outcomes during short-term follow-up, including emergency room (ER) visit, hospitalization, or death, were also assessed among the patients. Results: A total of 952 patients presenting with mRNA-VRCS were included in this study, with 89.7% receiving Pfizer-BioNTech and 10.3% receiving Moderna vaccines. The mean duration from vaccination to symptom was 5.6±7.5 days. VAEs, including acute myocarditis and acute pericarditis, were confirmed in 11 (1.2%) and 10 (1.1%) patients, respectively. The VAE group showed higher rates of dyspnea, echocardiography changes, and ST-T segment changes. During the short-term follow-up period of 3 months, the VAE group showed a higher hospitalization rate compared to the control group; there was no significant difference in ER visit (p=0.320) or mortality rates (p>0.999). Conclusion Amongst the patients who experienced mRNA-VRCS, the total incidence of VAEs, including acute myocarditis and pericarditis, was 2.2%. Patients with VAEs showed higher rates of dyspnea, echocardiographic changes, and ST-T segment changes compared to those without VAEs. With or without the cardiovascular events, the prognosis in patients with mRNA-VRCS was favorable.

Purpose: The number of patients presenting with vaccination-related cardiovascular symptoms after receiving mRNA vaccines (mRNA-VRCS) is increasing. We investigated the incidence of vaccine-related adverse events (VAEs), including myocarditis and pericarditis, in patients with mRNA-VRCS after receiving BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna vaccines. Materials and Methods: We retrospectively collected data on patients presenting with mRNA-VRCS who visited the outpatient clinic of two tertiary medical centers. Clinical characteristics, laboratory findings, echocardiographic findings, and electrocardiographic findings were evaluated. VAE was defined as myocarditis or pericarditis in patients after mRNA vaccination. Clinical outcomes during short-term follow-up, including emergency room (ER) visit, hospitalization, or death, were also assessed among the patients. Results: A total of 952 patients presenting with mRNA-VRCS were included in this study, with 89.7% receiving Pfizer-BioNTech and 10.3% receiving Moderna vaccines. The mean duration from vaccination to symptom was 5.6±7.5 days. VAEs, including acute myocarditis and acute pericarditis, were confirmed in 11 (1.2%) and 10 (1.1%) patients, respectively. The VAE group showed higher rates of dyspnea, echocardiography changes, and ST-T segment changes. During the short-term follow-up period of 3 months, the VAE group showed a higher hospitalization rate compared to the control group; there was no significant difference in ER visit (p=0.320) or mortality rates (p>0.999). Conclusion Amongst the patients who experienced mRNA-VRCS, the total incidence of VAEs, including acute myocarditis and pericarditis, was 2.2%. Patients with VAEs showed higher rates of dyspnea, echocardiographic changes, and ST-T segment changes compared to those without VAEs. With or without the cardiovascular events, the prognosis in patients with mRNA-VRCS was favorable.

Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.