A certain period of time has passed since the transition to the General Medicine residency system under the Japanese Medical Specialty Board and Family Medicine specialist training system by the Japan Primary Care Association. We have summarized the needs of residents identified in the survey, and detailed the activities to date and prospects of the Japanese Association of Family Physician Trainees, a self-help support organization, which is an official subcommittee of the Japan Primary Care Association, from the viewpoint of the residents. We believe that this paper will serve as a resource for the training of residents, help guide them under the new system, and help to improve the training system, considering evidence suggesting that information may not be reaching residents who need support.

BACKGROUND: Pyrethroid (PYR) insecticides are widely used for controlling various pests. There are two types that differ in terms of usage: agricultural-purpose PYR (agriculture-PYR) and hygiene purpose PYR (hygiene-PYRs). Few studies exist on the exposure to these chemicals in small children. In this study, we conducted biomonitoring of urinary pyrethroid metabolites in 1.5-year-old children throughout the year. METHODS: Study subjects were 1075 children participating in an Aichi regional sub-cohort of the Japan Environment and Children's Study as of 18-month health check-up. The concentrations of four specific hygiene-PYR metabolites including 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH₂-FB-Al), and five common metabolites of hygiene- and agriculture-PYRs including 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DCCA), were measured in urine samples extracted from soiled diapers using a triple quadrupole gas chromatograph-mass spectrometer. RESULTS: The highest detection frequencies were for 3PBA, followed by DCCA, 1R-trans-chrysanthemum dicarboxylic acid, and HOCH₂-FB-Al. Among the six metabolites, urinary concentrations were seasonally varied. However, this variation was not observed in the most studied PYR metabolite, 3PBA. Spearman's correlation analysis demonstrated a significant positive correlation between FB-Al and DCCA (r = 0.56) and HOCH₂-FB-Al and 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (r = 0.60). CONCLUSIONS This biomonitoring survey found widespread and seasonally specific exposure to multiple hygiene- and agriculture-PYRs in 1.5-year-old Japanese children.
Agriculture ; Child, Preschool ; Environmental Exposure/analysis* ; Humans ; Infant ; Insecticides ; Japan ; Mass Spectrometry ; Pyrethrins/urine*

Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear. Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021. Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset. Conclusion Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

Objective: To examine the relationship between the time constant of oxygen uptake kinetics during the onset of exercise (τVO2) estimated from a single exercise bout and that obtained from three averaged exercise bouts in individuals with stroke. Methods: Twenty participants with stroke performed three bouts of a constant-load pedaling exercise at approximately 80% of the workload corresponding to the ventilatory threshold to estimate τVO2. The VO2 data from the first trial of three bouts were used to estimate τVO2 for a single bout. Additionally, data collected from three bouts were ensemble-averaged to obtain τVO2 for three averaged bouts as the criterion. Results: There was a very high correlation between τVO2 for a single bout (34.8±14.0 seconds) and τVO2 for three averaged bouts (38.5±13.4 seconds) (r=0.926, p<0.001). However, τVO2 for a single bout was smaller than that for three averaged bouts (p=0.006). Conclusion τVO2 for a single bout could reflect the relative difference in τVO2 for three averaged bouts among individuals with stroke. However, it should be noted that τVO2 for a single bout may be underestimated compared to τVO2 for three averaged bouts.

Objective: To examine the relationship between the time constant of oxygen uptake kinetics during the onset of exercise (τVO2) estimated from a single exercise bout and that obtained from three averaged exercise bouts in individuals with stroke. Methods: Twenty participants with stroke performed three bouts of a constant-load pedaling exercise at approximately 80% of the workload corresponding to the ventilatory threshold to estimate τVO2. The VO2 data from the first trial of three bouts were used to estimate τVO2 for a single bout. Additionally, data collected from three bouts were ensemble-averaged to obtain τVO2 for three averaged bouts as the criterion. Results: There was a very high correlation between τVO2 for a single bout (34.8±14.0 seconds) and τVO2 for three averaged bouts (38.5±13.4 seconds) (r=0.926, p<0.001). However, τVO2 for a single bout was smaller than that for three averaged bouts (p=0.006). Conclusion τVO2 for a single bout could reflect the relative difference in τVO2 for three averaged bouts among individuals with stroke. However, it should be noted that τVO2 for a single bout may be underestimated compared to τVO2 for three averaged bouts.

BACKGROUND/AIMS: In this study, we aimed to evaluate the predictive value of localized stenosis of the main pancreatic duct (MPD) for early detection of pancreatic cancer.METHODS: Among 689 patients who underwent endoscopic retrograde pancreatography from January 2008 to September 2018, 19 patients with MPD findings were enrolled. These patients showed findings for indicating suspicious pancreatic cancer at an early stage (FiCE); FiCE was defined as a single, localized stenosis in the MPD without a detectable mass (using any other imaging methods) and without other pancreatic diseases, such as definite chronic pancreatitis, intraductal papillary mucinous neoplasm, and autoimmune pancreatitis. Final diagnoses were established by examining resected specimens or through follow-up examinations after an interval of >5 years.RESULTS: Among 19 patients with FiCE, 11 underwent surgical resection and 8 were evaluated after a >5-year observation period. The final diagnosis of the MPD stenosis was judged to be pancreatic cancer in 9 patients (47%), including 3 with intraepithelial cancer, and to be a non-neoplastic change in 10. The sensitivity, specificity, and accuracy of preoperative pancreatic juice cytology were 75%, 100%, and 88%, respectively.CONCLUSIONS: The predictive value of FiCE for pancreatic cancer prevalence was 47%. Histological confirmation with pancreatic juice cytology is necessary before surgical resection.
Cholangiopancreatography, Endoscopic Retrograde ; Constriction, Pathologic ; Diagnosis ; Follow-Up Studies ; Humans ; Mucins ; Pancreatic Diseases ; Pancreatic Ducts ; Pancreatic Juice ; Pancreatic Neoplasms ; Pancreatitis ; Pancreatitis, Chronic ; Prevalence ; Sensitivity and Specificity

The plasticizer di(2-ethylhexyl) phthalate (DEHP) has been widely used in the manufacture of polyvinyl chloride-containing products such as medical and consumer goods. Humans can easily be exposed to it because DEHP is ubiquitous in the environment. Recent research on the adverse effects of DEHP has focused on reproductive and developmental toxicity in rodents and/or humans. DEHP is a representative of the peroxisome proliferators. Therefore, peroxisome proliferator-activated receptor alpha (PPARα)-dependent pathways are the expected mode of action of several kinds of DEHP-induced toxicities. In this review, we summarize DEHP kinetics and its mechanisms of carcinogenicity and reproductive and developmental toxicity in relation to PPARα. Additionally, we give an overview of the impacts of science policy on exposure sources.
Animals ; Diethylhexyl Phthalate ; toxicity ; Environmental Pollutants ; toxicity ; Haplorhini ; Humans ; Mice ; PPAR alpha ; genetics ; metabolism ; Plasticizers ; toxicity ; Rats

BACKGROUND: Low-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. However, the inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is thus considered difficult to accurately assess OP exposure during pregnancy with single sampling. This study aimed to assess intra-individual variations of DAP concentrations and the reproducibility of the exposure dose categorization of OPs according to DAP concentration ranges in pregnant women in Japan. METHODS: Urine samples were collected from 62 non-smoking pregnant women (12-22 weeks of gestation) living in Aichi Prefecture, Japan. First morning void (FMV) and spot urine samples taken between lunch and dinner on the same day were collected on five different days during 2 weeks. The concentrations of DAP and creatinine in urine samples were measured using an ultra performance liquid chromatography with tandem mass spectrometry. Creatinine-adjusted and unadjusted concentrations were used for the intraclass correlation coefficient (ICC) calculations and surrogate category analyses. RESULTS: For all DAP metabolites, the creatinine-adjusted single ICCs exceeded 0.4, indicating moderate reliability. Overall, ICCs of spot urine samples taken in the afternoon were better than those taken as FMV. Surrogate category analyses showed that participants were categorized accurately into four exposure dose groups according to the quartile points. CONCLUSION This study indicated that a single urine sample taken in the afternoon may be useful in assessing OP exposure as long as the exposure is categorized into quartiles when conducting epidemiological studies in early to mid-pregnant women in Japan.
Adult ; Chromatography, Liquid ; Creatinine ; urine ; Environmental Exposure ; analysis ; Environmental Monitoring ; methods ; Environmental Pollutants ; urine ; Female ; Humans ; Japan ; Mass Spectrometry ; Organophosphates ; urine ; Pesticides ; urine ; Pregnancy ; Pregnant Women ; Young Adult

BACKGROUND/AIMS: This study aimed to identify the predictive factors for inaccurate endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) diagnosis of swollen lymph nodes without rapid on-site cytopathological evaluation. METHODS: Eighty-three consecutive patients who underwent EUS-FNA for abdominal or mediastinal lymph nodes from January 2008 to June 2017 were included from a prospectively maintained EUS-FNA database and retrospectively reviewed. The sensitivity, specificity, and accuracy of EUS-FNA for the detection of neoplastic diseases were calculated. Candidate factors for inaccurate diagnosis (lymph node size and location, needle type, puncture route, number of passes, and causative disease) were evaluated by comparison between accurately diagnosed cases and others. RESULTS: The final diagnosis of the punctured lymph node was classified as neoplastic (65 cases: a metastatic lymph node, malignant lymphoma, or Crow-Fukase syndrome) or non-neoplastic (18 cases: a reactive node or amyloidosis). The sensitivity, specificity, and accuracy were 83%, 94%, and 86%, respectively. On multivariate analyses, small size of the lymph node was the sole predictive factor for inaccurate EUS-FNA diagnosis with a significant difference (odds ratios, 19.8; 95% confidence intervals, 3.15–124; p=0.0015). CONCLUSIONS: The lymph node size of <16 mm was the only independent factor associated with inaccurate EUS-FNA diagnosis of swollen lymph nodes.
Diagnosis ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Endosonography ; Humans ; Lymph Nodes ; Lymphatic Diseases ; Lymphoma ; Multivariate Analysis ; Needles ; Prospective Studies ; Punctures ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity

BACKGROUND/AIMS: It is often difficult to manage acute cholecystitis after metal stent (MS) placement in unresectable malignant biliary strictures. The aim of this study was to evaluate the feasibility of endoscopic ultrasonography-guided gallbladder drainage (EUS-GBD) for acute cholecystitis. METHODS: The clinical outcomes of 10 patients who underwent EUS-GBD for acute cholecystitis after MS placement between January 2011 and August 2018 were retrospectively evaluated. The procedural outcomes of percutaneous transhepatic gallbladder drainage (PTGBD) with tube placement (n=11 cases) and aspiration (PTGBA) (n=27 cases) during the study period were evaluated as a reference. RESULTS: The technical success and clinical effectiveness rates of EUS-GBD were 90% (9/10) and 89% (8/9), respectively. Severe bile leakage that required surgical treatment occurred in one case. Acute cholecystitis recurred after stent dislocation in 38% (3/8) of the cases. Both PTGBD and PTGBA were technically successful in all cases without severe adverse events and clinically effective in 91% and 63% of the cases, respectively. CONCLUSIONS: EUS-GBD after MS placement was a feasible option for treating acute cholecystitis. However, it was a rescue technique following the established percutaneous intervention in the current setting because of the immature technical methodology, including dedicated devices, which need further development.
Bile ; Cholecystitis, Acute ; Constriction, Pathologic ; Dislocations ; Drainage ; Gallbladder ; Humans ; Retrospective Studies ; Stents ; Treatment Outcome