In 1996, our medical school introduced symposium-style learning that is focused on recent advances in medical science as a regular undergraduate program for 6th-year students. The goals of this program are as follows: 1) to teach that good scientific research is essential to support high-quality medical education and medical care, 2) to have students enjoy research in a way they cannot in the ordinary curriculum, and 3) to stimulate interest in research in medical students who may become researchers in the future. Although a long-term survey is needed to evaluate the effects of this kind of learning strategy, an analysis of questionnaires showed that it was effective for the intended purposes. Today, the content of medical education has become diversified, and the social demands on medicine have changed greatly. Thus, we believe it is necessary to develop an education program separately from traditional ones that are primarily oriented to transmission of knowledge.

BACKGROUNDSeveral studies have suggested that the exposure to cadmium (Cd) increased mortalities from renal diseases, cardiovascular diseases and malignant neoplasm, including lung cancer and prostate cancer among inhabitants living in Cd-polluted areas and factory workers. This study aimed to assess the influence of environmental exposure to Cd on long term outcome of inhabitants living in an area polluted by Cd.

METHODSA 22-year follow-up study was conducted with 3119 inhabitants (1403 men and 1716 women) living in the Cd polluted Kakehashi River basin in Japan. The subjects were divided into 4 groups according to the amount of urinary Cd level (< 3.0 µg/g creatinine (Cr), 3.0 - 4.9 µg/g Cr, 5.0 - 9.9 µg/g Cr, and ≥ 10.0 µg/g Cr). Mortality was calculated by the person-years method. Hazards ratios (HR) and 95% confidence intervals (CI) were assessed by the Cox's proportional hazard model.

RESULTSCompared with urinary Cd < 3.0 µg/g Cr group, the HR of 5.0 - 9.9 µg/g Cr and ≥ 10.0 µg/g Cr groups were significantly increased after adjustment for age in both sexes: 1.24 (95%CI 1.01 - 1.51) and 1.48 (95%CI 1.17 - 1.90) for men; 1.64 (95%CI 1.17 - 2.28) and 1.78 (95%CI 1.27 - 2.50) for women. The most frequent cause of death was malignant neoplasm in men and cardiovascular diseases in women. The significant increase in mortality risk for cardiovascular diseases was observed in the subjects with ≥ 10 µg/g Cr in both sexes: 1.79 for men (95%CI 1.02 - 3.12) and 2.38 for women (95%CI 1.11 - 5.07). When the subjects were divided into 2 categories (< 20 µg/g Cr and ≥ 20 µg/g Cr), the HR of the urinary Cd ≥ 20 µg/g Cr group for nephritis and nephrosis were 4.82 (95%CI 1.07 - 21.61) in men and 7.92 (95%CI 1.77 - 35.33) in women, respectively. The significant increase was not observed for malignant neoplasm.

CONCLUSIONThese results suggest a dose-response relationship between Cd body burden and mortality for cardiovascular diseases, cerebrovascular diseases and nephritis and nephrosis.

Aged ; Aged, 80 and over ; Cadmium ; toxicity ; Cardiovascular Diseases ; mortality ; Cerebrovascular Disorders ; mortality ; Environmental Exposure ; adverse effects ; Female ; Follow-Up Studies ; Hazardous Substances ; Humans ; Japan ; Male ; Middle Aged ; Nephritis ; mortality ; Nephrosis ; mortality ; Proportional Hazards Models ; Risk Factors

The mandibular third molars are usually located near the inferior alveolar nerve, and surgical extraction may damage this nerve causing dysesthesia. Recently, cone-beam computed tomography (CBCT) has become more widespread, facilitating the diagnosis of various diseases of the oral maxillofacial region. This study investigated dysesthesia of the inferior alveolar nerve following mandibular third molar extraction and the relationship between this complication and preoperative imaging findings. A total of 401 mandibular third molars were extracted from 345 patients with a mean age 33.9 ± 14.6 years (range, 16-81 years). All patients were evaluated by panoramic radiography, and 89 mandibular third molars were evaluated by CBCT. We classified the shape of the mandibular canal into 4 types based on its shape at the point closest to the mandibular third molars. The rate of dysesthesia after mandibular third molar extraction was 5.7% among patients considered to be at high risk who underwent CBCT, and 0.64% among patients considered to be at low risk. The mandibular third molars were not in contact with the inferior alveolar nerve in 51 of the patients who underwent CBCT. These results suggest that deformation of the mandibular canal may lead to dysesthesia following mandibular third molar extraction and that CBCT was useful for predicting the risk of this complication.

Purpose: This study was performed to determine the prognostic value of lymphocyte-to-CRP ratio after curative resection for hepatocellular carcinoma. Methods: Between July 2010 and October 2021, 173 consecutive patients (144 male, 29 female) who underwent surgical resection for pathologically confirmed hepatocellular carcinoma were included in this retrospective study. Cox regression analysis was used to evaluate the relationship between clinicopathological characteristics and recurrence-free survival (RFS) and overall survival (OS). A P-value of <0.05 was considered statistically significant. Results: The patients (mean age, 71 years) were stratified into high (≥9,500, n = 108) and low (<9,500, n = 65) lymphocyteto-CRP ratio groups. The low lymphocyte-to-CRP ratio group had significantly worse RFS and OS. Low lymphocyte-toCRP ratio (hazard ratio [HR], 1.865; 95% confidence interval [CI], 1.176–2.960; P = 0.008), multiple tumors (HR, 3.333; 95% CI, 2.042–5.343; P < 0.001), and microvascular invasion (HR, 1.934; 95% CI, 1.178–3.184; P = 0.009) were independently associated with RFS, whereas low albumin-to-globulin ratio (HR, 2.270; 95% CI, 1.074–4.868; P = 0.032), α-FP of ≥25 ng/mL (HR, 2.187; 95% CI, 1.115–4.259; P = 0.023), and poor tumor differentiation (HR, 2.781; 95% CI, 1.041–6.692; P = 0.042) were independently associated with OS. Lymphocyte-to-CRP ratio had a higher area under the curve (0.635) than other inflammation-based markers (0.51–0.63). Conclusion Lymphocyte-to-CRP ratio is superior to other inflammation-based markers as a predictor of RFS in patients with surgically resected hepatocellular carcinoma.

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: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%).Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions The present study demonstrated that ca-4F12-E6 was well-tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

 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.