Size-classified aerosol-bound heavy metals and their effects on human health risks in industrial and remote areas in Japan.

Airborne aerosols were collected in six size classes (PM<0.1, PM0.1-0.5, PM0.5-1, PM1-2.5, PM2.5-10 and PM>10) to investigate aerosol health risks in remote and industrial areas in Japan. We focused on heavy metals and their water-dispersed fractions. The average concentration of heavy metals was 18 ± 25-86 ± 48 ngm-3 for PM<0.1, 46 ± 19-154 ± 80 for PM0.5-1 ngm-3, 98 ± 49-422 ± 186 ngm-3 for PM1-2.5, 321 ± 305-1288 ± 727 ngm-3 for PM2.5-10 and 65 ± 52-914 ± 339 ngm-3 or PM>10, and these concentrations were higher in industrial areas. Heavy metals emitted from domestic anthropogenic sources were added to the long-range transport component of the aerosols. The water-dispersed fraction of heavy metals contained 3.3-40.1% of the total heavy metals in each size class. The relative contribution of Zn and other species (As, Cd, Cr, Ni, Pb, Mn, V and Cu) increased in the water-dispersed fraction. Smaller particles contained greater proportions of the water-dispersed heavy metal fraction. Carcinogenic risk (CR) and the hazard index (HI) were estimated for each size class. The CR of carcinogens was at acceptable levels (<1 ×10-6) for five particle size fractions. The HI values for carcinogens and noncarcinogens were also below acceptable levels (<1) for the same five size fractions. The estimated CR and HI values were dominated by contributions from the inhalation process.

Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections.

The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics and correlative analysis of an immunologically naïve SARS-CoV-2 clinical cohort from blood plasma of uninfected controls, mild, and severe infections. Consistent with previous observations, severe patient populations showed an elevation of pulmonary surfactant levels. Intriguingly, mild patients showed a statistically significant elevation in the carnosine dipeptidase modifying enzyme (CNDP1). Mild and severe patient populations showed a strong elevation in the metabolite L-cystine (oxidized form of the amino acid cysteine) and enzymes with roles in glutathione metabolism. Neutrophil extracellular traps (NETs) were observed in both mild and severe populations, and NET formation was higher in severe vs. mild samples. Our correlative analysis suggests a potential protective role for CNDP1 in suppressing PSPB release from the pulmonary space whereas NET formation correlates with increased PSPB levels and disease severity. In our discussion we put forward a possible model where NET formation drives pulmonary occlusions and CNDP1 promotes antioxidation, pleiotropic immune responses, and vasodilation by accelerating histamine synthesis.

Investigation of Japan Disaster Medical Assistance Team response guidelines assuming catastrophic damage from a Nankai Trough earthquake.

Aim: Transporting critically ill patients outside of disaster-affected areas for treatment is an important activity of Japan Disaster Medical Assistance Teams (DMATs). We investigated whether this activity is possible after possible catastrophic damage from a Nankai Trough earthquake. Methods: Japan was divided into three areas based on the level of predicted damage (definitely, possibly, and non-affected areas). A survey of DMATs and the locations of emergency base hospitals and intensive care units (ICUs) in each area was carried out, and the ability to support disaster areas was investigated. Next, a survey of wide-area medical transport by Self-Defense Force aircraft and the medical transport abilities of helicopter ambulances was carried out. The numbers of ICU beds in each area were compared, and the capacity to accept patients was investigated. Finally, subjects for further study were examined. Results: The number of DMATs that could be sent from non-affected areas was insufficient. The number of patients that can be transported by Self-Defense Force aircraft and helicopter ambulance during the first 3 days was determined to be 1,443. The number of patients that can be accepted by ICUs in non-affected areas was insufficient. A system needs to be developed to provide medical treatment for critically ill patients within disaster areas during the acute phase. This will require DMAT operational reforms and the creation of logistics systems such as the supply of resources for earthquake-reinforced hospitals. Conclusion: In addition to patient transport, systems to provide medical care inside disaster-affected areas are needed.

[Combination chemotherapy of S-1 and CPT-11 for advanced recurrent gastric cancer].

We performed combination chemotherapy using S-1 and CPT-11 for advanced and recurrent stomach carcinoma in order to study the clinical efficacy thereof. The subjects comprised 13 patients aged 55 to 78 with a PS of 0 to 2, who had histologically confirmed unresectable stomach carcinoma or who had undergone a non curative resection with postoperative recurrence, all having measurable or assessable lesions with no severe damage in the principal organ, and from whom informed consent in writing had been obtained. 80 to 120 mg/day of S-1 were orally administered daily for 21 days according to the body surface area. 60 mg/m2 of CPT-11 was administered on Days 1 and 15. After the administration of S-1 for 3 weeks, from 1- to 2-week-long drug holidays were provided, thereby establishing a total of 4 to 5 weeks as 1 course. This was repeated as many times as possible. Thirteen subjects were registered during the period from November 2001 to February 2004. The details thereof are as follows: 9 male subjects and 4 female subjects with a median age of 65 years, wherein 1 subject had a PS of 0, 3 subjects had a PS of 1, and 9 subjects had a PS of 2. The results for all of the subjects showed that 5 subjects had PR, and the response rate was 38%. Grade 3 or higher adverse events consisted of leucopenia in 38.5%, neutropenia in 46.2%, anemia in 15.4%, and diarrhea in 7.7%. The median survival time (MST) for all of the subjects was 259 days. Specifically, the MST was 248 days for the subjects with a PS of 2 for whom 2 drugs were concomitantly used, and it was equal or longer for the subjects with a PS of 2 who were treated under the sole regimen of S-1. A review of this study showed that side effects were more frequently observed in the subjects with a PS of 2 than in those with a PS of 0 to 1. Furthermore, the average number of courses that were administered to the subjects with a PS of 0 to 1 was 8.5, against 3.6 courses on average in subjects with a PS of 2, thus showing a significant difference between the 2 groups. According to the above results, it is believed that there is a difference in the tolerability of the anticancer drugs between subjects with a PS of 0 to 1 and those with a PS of 2. It is also considered necessary to adjust the dosage of the anticancer drugs and the dosing period for patients with a PS of 2 when preparing a chemotherapeutic regimen for digestive carcinoma, including stomach carcinoma. The present regimen will be further studied to evaluate its potential use after second-line therapy for advanced and recurrent stomach carcinoma.