BACKGROUND: Organic chemicals have been known to cause allergic diseases such as bronchial asthma and hypersensitivity pneumonitis; however, the possibility that they do not cause irreversible pulmonary fibrosis has not been considered. Polyacrylic acid (PAA), an organic chemical, has caused irreversible progressive pulmonary fibrosis in exposed workers, indicating its potential to induce pulmonary inflammation and fibrosis. Although intratracheal instillation studies are commonly used for evaluating lung pathology, traditional methods face challenges with chemical substances, particularly nanoparticles, which tend to aggregate in suspension and prevent uniform pulmonary distribution. Such aggregation alters the qualitative and quantitative responses to lung injury, limiting accurate assessment of lung pathology. To overcome this limitation, we developed a 'molecular dispersion method' that uses pH modification to negative charges to PAA particles, maintaining their dispersion. Using this method, we investigated the effects of PAA on pulmonary inflammation and fibrosis in a rat model. METHODS: F344 rats were intratracheally instilled with PAA using molecular dispersion (0.1 mg/rat, 1.0 mg/rat), PAA without molecular dispersion (1.0 mg/rat), and normal saline (control group). Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses. RESULTS: PAA caused persistent increases in neutrophil influx in the bronchoalveolar lavage fluid (BALF) from 3 days to 1 month following instillation. In histopathological findings, the group with molecular dispersion had almost no inflammatory masses in the lung tissue compared to the group without molecular dispersion, and exhibited relatively uniform dispersion. CONCLUSION Intratracheal instillation of dispersed PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA might have pulmonary inflammogenicity and fibrogenicity. Intrapulmonary dispersion of PAA particles following intratracheal instillation studies using the molecular dispersion method was similar to that following inhalation studies.
Animals ; Rats, Inbred F344 ; Acrylic Resins/adverse effects* ; Rats ; Inhalation Exposure/adverse effects* ; Male ; Pulmonary Fibrosis/pathology* ; Pneumonia/pathology* ; Lung/pathology* ; Bronchoalveolar Lavage Fluid/cytology*

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9–52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%–88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Objective: This study aimed to elucidate the factors that affect medication adherence in outpatients with depression using multivariate analysis.Methods: A web-based survey on medication adherence, medication attitude (Drug Attitude Inventory-10; DAI-10), medication self-management, and satisfaction with the prescribing physician/pharmacy for outpatients with depression was conducted in January 2018. T-tests and path analysis were performed to evaluate comparisons of responses based on gender, high/low importance of medication guidance, high/low intention to consult, and high/low frequency of consultations.Results: For mean scores, no significant difference was observed between males and females according to a t-test. In terms of the importance of medication guidance, the high importance group had significantly higher prescribing physician/pharmacy satisfaction and better self-management. In terms of intention to consult, respondents with high intention to consult had significantly higher scores on the DAI-10, better self-management, and higher prescribing physician/pharmacy satisfaction. In terms of frequency of consultations, only pharmacy satisfaction was significantly higher in the high-frequency group. Path analysis revealed that, in general, adherence was influenced by medication attitude and self-management, and prescribing physician/pharmacy satisfaction and self-management were influenced by medication attitude. In the intergroup comparison, pharmacy satisfaction did not affect medication adherence in males or the group with low importance of medication guidance. In addition, medication attitude did not affect adherence only in the non-consultation group.Discussion: These results suggest that it is necessary to improve the medication support measures at pharmacies for outpatients with depression. Furthermore, in order for the measures to improve medication attitudes and adherence to be effective, it is necessary for patients to understand the benefits and importance of using pharmacists effectively, including medication support and consultation, and to be actively involved in the maintenance and promotion of patients' health.

Objective: Human papillomavirus subtypes are predictive indicators of cervical intraepithelial neoplasia (CIN) progression. While colposcopy is also an essential part of cervical cancer prevention, its accuracy and reproducibility are limited because of subjective evaluation. This study aimed to develop an artificial intelligence (AI) algorithm that can accurately detect the optimal lesion associated with prognosis using colposcopic images of CIN2 patients by utilizing objective AI diagnosis. Methods: We identified colposcopic findings associated with the prognosis of patients with CIN2. We developed a convolutional neural network that can automatically detect the rate of high-grade lesions in the uterovaginal area in 12 segments. We finally evaluated the detection accuracy of our AI algorithm compared with the scores by multiple gynecologic oncologists. Results: High-grade lesion occupancy in the uterovaginal area detected by senior colposcopists was significantly correlated with the prognosis of patients with CIN2. The detection rate for high-grade lesions in 12 segments of the uterovaginal area by the AI system was 62.1% for recall, and the overall correct response rate was 89.7%. Moreover, the percentage of high-grade lesions detected by the AI system was significantly correlated with the rate detected by multiple gynecologic senior oncologists (r=0.61). Conclusion Our novel AI algorithm can accurately determine high-grade lesions associated with prognosis on colposcopic images, and these results provide an insight into the additional utility of colposcopy for the management of patients with CIN2.

BACKGROUND: Heat shock protein 70 (HSP70) exhibits protective effects against ultraviolet (UV)-induced premature skin aging. A standardized extract of Asparagus officinalis stem (EAS) is produced as a novel and unique functional food that induces HSP70 cellular expression. To elucidate the anti-photoaging potencies of EAS, we examined its effects on HSP70 expression levels in UV-B-irradiated normal human dermal fibroblasts (NHDFs). METHODS: NHDFs were treated with 1 mg/mL of EAS or dextrin (vehicle control) prior to UV-B irradiation (20 mJ/cm). After culturing NHDFs for different time periods, HSP70 mRNA and protein levels were analyzed using real-time polymerase chain reaction and western blotting, respectively. RESULTS: UV-B-irradiated NHDFs showed reduced HSP70 mRNA levels after 1-6 h of culture, which were recovered after 24 h of culture. Treatment with EAS alone for 24 h increased HSP70 mRNA levels in the NHDFs, but the increase was not reflected in its protein levels. On the other hand, pretreatment with EAS abolished the UV-B irradiation-induced reduction in HSP70 expression at both mRNA and protein levels. These results suggest that EAS is capable to preserve HSP70 quantity in UV-B-irradiated NHDFs. CONCLUSIONS EAS exhibits anti-photoaging potencies by preventing the reduction in HSP70 expression in UV-irradiated dermal fibroblasts.
Asparagus Plant ; Cells, Cultured ; Female ; Fibroblasts ; drug effects ; radiation effects ; HSP70 Heat-Shock Proteins ; biosynthesis ; Humans ; Middle Aged ; Plant Extracts ; pharmacology ; Polymerase Chain Reaction ; Skin ; drug effects ; radiation effects ; Skin Aging ; drug effects ; radiation effects ; Telomere ; metabolism ; Ultraviolet Rays ; adverse effects

Endovascular aortic aneurysm repair using stent graft (SG) for both thoracic and abdominal aortic aneurysms (SG therapy) rapidly became widespread in Japan because of its relatively low invasiveness. Pre- and postoperative contrast enhanced CT are mandatory in SG therapy and angiography is required during SG therapy. Therefore contrast induced nephropathy (CIN) might occur after SG therapy. In our hospital, a renal protection protocol (oral N-acetylcysteine, perioperative normal saline infusion and bicarbonate infusion during SG therapy) was introduced in June 2010. In this report, the effect of the renal protection protocol on renal function after SG therapy was evaluated. During May 2008 and March 2012, 229 patients underwent SG therapy in our hospital. Serum creatinine (CRTN) was higher than 1.5 mg/dl and estimated glomerular filtration rate (eGFR) was less than 50 ml/min/1.73 m² in 26 patients. In these 26 patients, the renal protection protocol was applied in 15 patients (group P) and group P was compared with the 11 patients without renal protection protocol (group N). Also the relationship between CIN occurrence and preoperative renal function was evaluated in 192 patients who did not receive the renal protection protocol. CIN was defined as more than 25% or 0.5 mg/dl increase of CRTN based on the European Guidelines. As renal protection protocol, N-acetylcysteine (600 mg) was given 4 times every 12 h. Normal saline infusion was started on the evening of the day before surgery at the rate of 50 ml/h and was continued until 1h before surgery. Sodium bicarbonate solution (151 mEq/l) was started 1 h before surgery at the rate of 180 ml/h and the infusion rate was decreased to 60 ml/h during surgery. After surgery, 1,000 ml of normal saline was given at a rate of 60 ml/h. In group N, CRTN increased 1 and 3 days after SG therapy and returned to baseline level 6 days after SG therapy. On the other hand, CRTN was lower than baseline after SG therapy in group P. At 3 days after SG therapy, the percent change of CRTN component with baseline level was significantly lower in group P (14.5±19.1% in group N, -3.7±15.8% in group P, p=0.014). CIN occurrence tended to be more in group N (45% in group N, 7% in group P, p=0.054). Among the 192 patients without the renal protection protocol, CIN occurred in 16 patients (29.1%) out of 55 patients with preoperative CRTN≥1.0 mg/dl and eGFR≤50 ml/min/1.73 m², however CIN occurred in only 1 patient (0.7%) among 137 patients with preoperative renal function out of this range (p<0.001). Renal protection protocol seemed to be effective to prevent CIN after SG therapy. Renal protection might be useful for patients with a CRTN≧1.0 mg/dl and eGFR≦50 ml/min/1.73 m².

We report a case of thoracic endovascular aortic repair (TEVAR) with a fenestrated stent graft for ulcer-like projection (ULP) of the proximal anastomosis after total arch replacement (TAR) for acute type A aortic dissection (DAA). A 73-year-old woman with a history of surgical resection of a left atrial myxoma in January 2009 underwent TAR for DAA in November 2011. The contrast enhanced CT (CE-CT) 72 days after TAR revealed two ULPs anterior and posterior to the proximal anastomosis. Surgical repair would be difficult because of the history of cardiac and aortic surgery, therefore TEVAR with a fenestrated stent graft was performed. The postoperative course was uneventful and she was discharged on the 8th postoperative day. The CE-CT 3 months after TEVAR showed almost completely thrombosed ULPs. Endovascular repair with fenestrated stent graft for the proximal anastomotic ULP can be a useful and effective treatment.

Endovascular repair for abdominal aortic aneurysm (EVAR) has become widespread in Japan because of its low invasiveness. However adequate proximal neck length is required for EVAR. Unfortunately the surgical mortality of para-renal aortic aneurysm cases has been higher than that of infrarenal aortic aneurysm cases, especially in high-risk patients. A manufacture-modified fenestrated Zenith stent graft system has already been developed, however this new device is not yet available in Japan. Furthermore this device could not be used in an emergency situation because it takes 2-3 weeks for preparation. Therefore we introduced a surgeon-modified fenestrated Zenith stent graft (fenestrated Zenith) system in December 2010 for patients with a proximal neck length of 5-10 mm. The fenestrated Zenith was not indicated if the supra-renal angle and proximal neck angle exceeded 35°. From May 2007 to February 2012, abdominal aortic aneurysms (AAA) with a short neck were repaired with fenestrated Zenith in 11 high-risk patients (group Fene), and AAAs with a proximal neck length of more than 15 mm were repaired with a standard Zenith in 43 patients (group IFU). There were two ruptured AAA in the Fene group. Proximal neck length was significantly shorter in the Fene group (5.5±1.4 mm in the Fene group, 26.4±9.5 mm in the IFU group, p<0.0001) and proximal neck angle was significantly less in the Fene group (20±13° in the Fene group, 36±18° in the IFU group, p=0.008). The Zenith stentgraft system was deployed successfully in all patients. The frequency of type Ia endoleak detected by angiography after stent graft deployment and balloon attachment did not differ significantly (36% in the Fene group 26% in the IFU group, p=0.475) and the frequency of Palmaz stent requirement for type Ia endoleak which persisted after 10 min of additional balloon attachment also did not differ significantly (27% in Fene group, 9% in IFU group). All fenestrated renal arteries were shown to be patent by angiography. There was no hospital death despite 2 cases of ruptured AAA, nor were these major complications in either group. Serum creatinine levels at 1, 3, 6 and 30 days after EVAR did not differ significantly between the 2 groups. In 9 out of 11 patients, only type II endoleaks were detected and aneurysm shrinkage tended to be more in Fene group (9.9±5.7 mm in Fene group, 5.4±6.1 mm in IFU group, p=0.062) on enhanced CT 6 months after EVAR. Also all fenestrated renal arteries were patent in these 9 patients. The surgeon-modified fenestrated Zenith system seemed to be effective for AAA patients with short proximal necks, but long term follow up is mandatory.

The results of endovascular abdominal aortic aneurysm repair (EVAR) for severe neck angulation with an Excluder were evaluated. We performed EVAR in 51 patients, using an Excluder, from September 2007 to September 2011. The angle between proximal neck and the aneurysm (Angle) was less than 61° in 31 patients (Group I), 61-90° in 13 patients (Group II) and more than 90° in 7 patients (Group III). In Groups I and II, the angled proximal neck was straightened with a stiff guide wire and a Trunkipsilateral device was deployed slowly (aortic modification technique). In Group III, the device modification technique was applied. In this technique, the stiff guide wire was inserted in the aortic root. The Trunkipsilateral device was bent to the contra lateral limb side and was inserted into the aorta. The stiff guide wire was pushed in with a fulcrum at the aortic valve. This procedure resulted in bending of the wire and the trunk-ipsilteral device became parallel to the proximal neck. The renal artery position was confirmed on angiographys and the main body was deployed slowly. We performed angiography after planned device deployment to evaluated Type Ia endoleak, and if it was observed, an additional procedure such as Aortic Extender or Palmaz XL stent deployment was performed and the Type Ia endoleak was evaluated during the procedure by completion angiography. The Angle change was measured by enhanced CT at 7 days and 6 month after EVAR. The Angle were 97-137° in Group III. The frequency of Type Ia endoleak after planned device deployment (35% in Group I, 55% in Group II and 17% in Group III), additional procedure for Type Ia endoleak (29% in Group I, 23% in Group II and 14% in Group III) and Type Ia endoleak by completion angiography (0% in Group I, 8% in Group II and 14% in Group III) did not differ significantly between the 3 groups. When Group I was sub divided into those with Angle less than 41° (Group Ia, 15 patients) and those with an Angle from 41 to 60° (Group Ib, 16 patients), Type Ia endoleak after planned device deployment (18% in Group Ia, 63% in Group Ib) was significantly more frequent in Group Ib and the additional procedure for Type Ia endoleak (7% in Group Ia, 50% in Group Ib) was more frequent in Group Ib. The Angle significantly decreased 7 days after EVAR and did not change thereafter in all 3 groups. EVAR with an Excluder for severe neck angulation was feasible by device modification with the bending technique. This technique might be useful for patients with an Angle of more than 41°.

 Hot sprigs elements and balneological effects of Tokyo 23 wards, which is not recognized as hot spring region were considered. The density of the hot spring’s source in this region is high compared to other parts of the country. Moreover, a useful element and temperature for the balneological treatment was confirmed by the hot springs with deep digging in a lot of places.  The hot springs in Tokyo can be classified into the NaCl strong salt hot springs, NaHCO3, and the sodium metasilicates. The strong Na-Cl (salt) springs are recognized in hot springs found by deep digging, and exists everywhere in Tokyo. The hot springs of the NaHCO3 are localized in Ohta ward by moderate depth digging. The hot springs including with the rich sodium metasilicates in Ohta ward by shallow digging. If the hot springs in Tokyo are to be used the balneologically, the following effects are expected.  Thermal and warm keeping effects can be expected from the strong Na-Cl (salt) springs. Cleanness and smoothing effects of the skin can be expected of NaHCO3. Hyperkeratosis of the skin can be expected from rich sodium metasilicates.