Tumor necrosis factor alpha-gene therapy for an established murine melanoma using RGD (Arg-Gly-Asp) fiber-mutant adenovirus vectors.

Although adenovirus vectors (Ad) provide high-level transduction efficacy to many cell types, extremely high doses of Ad are required for sufficient gene transduction into several tumors, including melanoma. Here, we demonstrated that the expression of coxsackie-adenovirus receptor, a primitive Ad-receptor, was very low in murine and human melanoma cells. We also found that fiber-mutant Ad containing the Arg-Gly-Asp (RGD) sequence in the fiber knob remarkably augmented gene transduction efficacy in melanoma cells by targeting alpha(v)-integrins. In addition, intratumoral injection of RGD fiber-mutant Ad containing the tumor necrosis factor alpha gene (Ad-RGD-TNFalpha) revealed dramatic anti-tumor efficacy through hemolytic necrosis in an established murine B16 BL6 melanoma model. Ad-RGD-TNFalpha required one-tenth the dosage of Ad-TNFalpha to induce an equal therapeutic effect. These results suggest that alpha(v)-integrin-targeted Ad will be a very powerful tool for the advancement of melanoma gene therapy.     

Urinary cadmium excretion is correlated with calcaneal bone mass in Japanese women living in an urban area

Nine hundred eight women aged 40-88 years living in a non-Cd-polluted area in Japan were analyzed for urinary cadmium (Cd), N-acetyl-beta-D-glucosaminidase (NAG) activity, beta(2)-microglobulin (B2MG) concentration, and for the stiffness index (STIFF) of calcaneal bone using an ultrasound method. The urinary Cd in the subjects, with a mean and range of 2.87 and 0.25-11.4 microg/g creatinine, respectively, showed a significant correlation with NAG but not with B2MG. STIFF was significantly inversely correlated with urinary Cd, and the association remained significant after adjusting for age, body weight, and menstrual status, suggesting a significant effect of Cd on the bone loss in these subjects without signs of Cd-induced kidney damage. A two-fold increase in urinary Cd was accompanied by a decrease in STIFF corresponding to a 1.7-year rise in age. These results emphasize the need for reassessment of the significance of Cd exposure in the general Japanese population.     

Association between maternal gestational diabetes mellitus and high‐sensitivity C‐reactive protein levels in 8‐year‐old children: The Yamanashi Adjunct Study of the Japan Environment and Children’s Study (JECS)

Gestational diabetes mellitus (GDM) is one of the most common pregnancy‐related complications; it is associated with adverse pregnancy outcomes and metabolic disorders in offspring, consistent with the concept of the developmental origins of health and disease. This cohort study of women without diabetes (n = 761), who were part of the Yamanashi Adjunct Study of the Japan Environment and Children’s Study, aimed to explore the associations between maternal GDM and their offspring’s level of high‐sensitivity C‐reactive protein (hsCRP), a biomarker of inflammatory and cardiovascular diseases. We analyzed the associations between GDM and the offspring’s hsCRP levels using a multiple logistic regression model. A mother with GDM significantly increased the risk for high hsCRP level by 4.07‐fold (≥2.0 mg/L) in the child. As such, maternal GDM was significantly associated with increased serum hsCRP levels in 8‐year‐old children.     

Mealtime Regularity Is Associated with Dietary Balance among Preschool Children in Japan—A Study of Lifestyle Changes during the COVID-19 Pandemic

The novel coronavirus-19 (COVID-19) pandemic has considerably impacted children’s lives. The aim of this study was to determine whether the pandemic affected mealtime regularity among preschool children and whether maintaining regular mealtimes or changes in mealtime regularity during the pandemic were related to dietary balance, including chronological relationships. This online cross-sectional survey involving individuals registered with a company that provides meals to children aged 2−6 years was conducted in February 2021. Using a 40-point scale, a healthy diet score (HDS) was developed to evaluate children’s dietary balance. The participants were divided into four groups based on their responses, and multiple regression analyses were performed with the HDS as the dependent variable. Maintaining regular mealtimes was associated with practices such as waking and going to bed earlier, less snacking, and eating breakfast every day. Even after adjusting for basic attributes, lifestyle habits, household circumstances, and other factors, regular mealtimes were still positively correlated with the HDS. These findings indicate that maintaining regular mealtimes is associated with higher HDS scores and better lifestyle habits. Furthermore, as the changed HDS was higher in the group whose mealtimes became regular during the pandemic, adopting regular mealtimes may lead to a more balanced diet.     

Prognostic Factors in Endodontic Surgery Using an Endoscope: A 1 Year Retrospective Cohort Study

This retrospective study clarified the success rate of endoscopic endodontic surgeries and identified predictors accounting for successful surgeries. In this retrospective study, 242 patients (90 males, 152 females) who underwent endoscopic endodontic surgery at a single general hospital and were diagnosed through follow-up one year later were included. Risk factors were categorized into attributes, general health, anatomy, and surgery. Then, the correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and factors related to the surgical prognosis factor were identified. The success rate of endodontic surgery was 95.3%, showing that it was a highly predictable treatment. The top three correlation coefficients were post, age, and perilesional sclerotic signs. Among them, the presence of posts was the highest, compared with the odds ratio, which was 9.592. This retrospective study revealed the success rate and risk factors accounting for endoscopic endodontic surgeries. Among the selected clinical variables, the presence of posts was the most decisive risk factor determining the success of endodontic surgeries.     

Beneficial Effect of Partial Portal Decompression Using the Inferior Mesenteric Vein for Intractable Gastroesophageal Variceal Bleeding in Patients With Liver Cirrhosis

BACKGROUND: Use of the inferior mesenteric vein (IMV) for partial portal decompression has not been recommended as a first-line option for intractable gastroesophageal variceal bleeding because of the thin diameter of the vein. Although these indications remain relevant, few reports have compared partial portal decompression using the IMV with other therapies. We propose that partial portal decompression using the IMV is a useful alternative treatment for intractable variceal bleeding. METHODS: We performed partial portal decompression using the IMV in eight patients with intractable variceal bleeding that had been uncontrolled using medical and endoscopic therapies. All patients were classified into Child's class B or C. The surgical data, morbidity, and mortality were assessed. RESULTS: Mean portal venous pressure significantly decreased from 26.9 +/- 2.0 mmHg before the surgery to 19.8 +/- 3.9 mmHg after the surgery. The operative mortality rate was 0%. The mean duration of hospital stay was 25.5 +/- 13.3 days. Although one patient experienced recurrent bleeding, shunt patency was well maintained in all patients during the follow-up period (mean 28.9 +/- 14.1 months). Six patients are still alive and well without ascites or hepatic encephalopathy. Two of the Child's class C patients who underwent emergency shunt died owing to hepatic decompensation. CONCLUSION: Partial portal decompression using the IMV can be a safe, effective way to treat intractable variceal bleeding in patients with liver cirrhosis. However, use of the shunt procedure may have the most survival benefits for cirrhotic patients with preserved liver function.     

Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome

Background

Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited.

The formation of intracellular glyceraldehyde-derived advanced glycation end-products and cytotoxicity

Background  

Nonalcoholic steatohepatitis (NASH) is a feature of metabolic syndrome. Advanced glycation end-products (AGEs) are formed by the Maillard reaction, which contributes to aging and to certain pathological complications of diabetes. A recent study has suggested that glyceraldehyde-derived AGEs (Glycer-AGEs) are elevated in the sera of patients with NASH. Furthermore, immunohistochemistry of Glycer-AGEs showed intense staining in the livers of patients with NASH. The present study aimed to examine the effect of intracellular Glycer-AGEs on hepatocellular carcinoma (Hep3B) cells.