Complete genome sequence of Paraburkholderia terrae strain KU-46, a 2,4-dinitrophenol-degrading bacterium.

Paraburkholderia terrae strain KU-46 has been studied for its capability to degrade 2,4-dinitrophenol. Here, we present the complete 10,833,180bp genome of this microorganism, comprising five circular chromosomes housing 9,797 protein-coding sequences. The genes responsible for 2,4-dinitrophenol and 4-nitrophenol degradation are located on chromosome 2.

Precise microbiome engineering using natural and synthetic bacteriophages targeting an artificial bacterial consortium.

In natural microbiomes, microorganisms interact with each other and exhibit diverse functions. Microbiome engineering, which enables bacterial knockdown, is a promising method to elucidate the functions of targeted bacteria in microbiomes. However, few methods to selectively kill target microorganisms in the microbiome without affecting the growth of nontarget microorganisms are available. In this study, we focused on the host-specific lytic ability of virulent phages and validated their potency for precise microbiome engineering. In an artificial microbiome consisting of Escherichia coli, Pseudomonas putida, Bacillus subtilis, and Lactiplantibacillus plantarum, the addition of bacteriophages infecting their respective host strains specifically reduced the number of these bacteria more than 102 orders. Remarkably, the reduction in target bacteria did not affect the growth of nontarget bacteria, indicating that bacteriophages were effective tools for precise microbiome engineering. Moreover, a virulent derivative of the λ phage was synthesized from prophage DNA in the genome of λ lysogen by in vivo DNA assembly and phage-rebooting techniques, and E. coli-targeted microbiome engineering was achieved. These results propose a novel approach for precise microbiome engineering using bacteriophages, in which virulent phages are synthesized from prophage DNA in lysogenic strains without isolating phages from environmental samples.

Medical care priorities of community-dwelling older adults according to three dimensions of quality of life: Quality of daily living, satisfaction and happiness from birth to death, and human vitality.

AIM: Although the maintenance and improvement of quality of life (QoL) through holistic care are important in geriatric medical care, care priorities might differ depending on three essential aspects of QoL: the quality of daily living, satisfaction and happiness from birth to death, and human vitality, which are "Seikatsu," "Jinsei," "Seimei" in Japanese, respectively. We aimed to clarify these priorities in terms of medical care and examined how the definitions of QoL affected these priorities' rankings. METHODS: This cross-sectional study involved community-dwelling older adults aged ≥65 years living in Kashiwa City, Chiba Prefecture, Japan. The number of participants was 1550 (mean age, 76.1 ± 5.8 years; 699 women [45.1%]). A self-administered questionnaire distributed in advance was used to rank 12 items sought in medical care. Participants were randomly assigned to one of three groups and sent the corresponding questionnaire, which differed only in the definition of QoL. RESULTS: The top priorities for medical care were "effective treatment of illness," "improvement of physical function," and "maintaining a high level of activity." When QoL was defined as "the quality of daily living, satisfaction and happiness from birth to death, and human vitality," participants were significantly more likely to rank QoL improvement as one of the top three items (adjusted odds ratio, 1.46; 95% confidence interval, 1.03-2.05). CONCLUSIONS: As a medical care priority, older adults desire improvement of multidimensional elements of life, including human vitality. Health care providers should consider this when making medical care decisions. Geriatr Gerontol Int 2024; 24: 493-498.

IgG4-Related Disease Complicated with Diffuse and Chronic Gastrointestinal Inflammation Leading to Small Intestinal Perforation.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4, IgG4+ cell infiltration, storiform fibrosis, and obliterative phlebitis. While IgG4-RD can affect various organs, gastrointestinal tract involvement is less common. Here, we report a 70-year-old female with IgG4-RD complicated with diffuse and chronic gastrointestinal inflammation which led to small intestinal perforation. She had been suffering from anorexia, abdominal pain, vomiting, and diarrhea, and hospitalized due to recurrent ileus. Consequently, she was referred due to small intestinal perforation required for surgical intervention. Pathology revealed acute and chronic inflammation with massive IgG4+ plasmacytes infiltration into mucosa of the small intestine, and ischemic change secondarily caused by chronic inflammation. Random biopsies from the mucosa of stomach, duodenum, ileum, and colon, also revealed diffuse and massive IgG4+ plasmacytes infiltration in stomach, duodenum, small intestine, and colon. She was diagnosed with IgG4-RD based on the pathological findings and elevated serum IgG4 levels. Glucocorticoid rapidly ameliorated the symptoms. IgG4-RD may cause gastrointestinal manifestations and histopathological assessment should be considered, even in the absence of specific characteristics of IgG4-RD.

Prevalence of oral frailty and its association with dietary variety, social engagement, and physical frailty: Results from the Oral Frailty 5-Item Checklist.

AIM: This cross-sectional study had two aims: to assess the prevalence of oral frailty (OF), according to the Oral Frailty 5-Item Checklist (OF-5), among community-dwelling older adults; and to examine the associations among oral frailty, dietary variety, social engagement, and physical frailty. METHODS: We pooled data from two population-based studies (the Otassha Study and the Itabashi Longitudinal Study on Aging). With the OF-5, OF is characterized by the presence of two or more of the following: (i) fewer teeth, (ii) difficulty in chewing, (iii) difficulty in swallowing, (iv) dry mouth, and (v) low articulatory oral motor skills. We calculated the OF prevalence for each sex. We assessed dietary variety, social engagement, and physical frailty. Generalized structural equation modeling was employed to investigate the associations among oral frailty, low dietary variety (dietary variety score ≤3), social isolation (Lubben Social Network Scale score <12), and physical frailty (Japanese version of the Cardiovascular Health Study score ≥3). RESULTS: A total of 1206 individuals (626 women and 580 men) with a mean age of 74.7 years were included. The prevalence of OF was 36.7%, and it increased with age; however, there was no significant sex difference. OF was significantly indirectly associated with physical frailty via low dietary variety (odds ratio, 1.43; 95% confidence interval, 1.04-1.97) and social isolation (odds ratio, 1.42; 95% confidence interval, 1.04-1.94). CONCLUSIONS: Two of five community-dwelling older adults exhibited OF. Low dietary variety and social isolation are potential underlying mechanisms through which OF is indirectly associated with physical frailty. Geriatr Gerontol Int 2024; 24: 371-377.

Benefit of a laparoscopic jejunostomy feeding catheter insertion to prevent bowel obstruction associated with feeding jejunostomy after esophagectomy.

The placement of a jejunostomy catheter during esophagectomy may cause postoperative bowel obstruction. The proximity of the jejunostomy site to the midline might be associated with bowel obstruction, and we have introduced laparoscopic jejunostomy (Lap-J) to reduce jejunostomy's left lateral gap. We evaluated 92 patients who underwent esophagectomy for esophageal cancer between February 2013 and August 2022 to clarify the benefits of Lap-J compared to other methods. The patients were classified into two groups according to the method of feeding catheter insertion: jejunostomy via small laparotomy (J group, n = 75), and laparoscopic jejunostomy (Lap-J group, n = 17). Surgery for bowel obstruction associated with the feeding jejunostomy catheter (BOFJ) was performed on 11 in the J group. Comparing the J and Lap-J groups, the distance between the jejunostomy and midline was significantly longer in the Lap-J group (50 mm vs. 102 mm; P < 0.001). Regarding surgery for BOFJ, the distance between the jejunostomy and midline was significantly shorter in the surgery group than in the non-surgery group (43 mm vs. 52 mm; P = 0.049). During esophagectomy, Lap-J can prevent BOFJ by placing the jejunostomy site at the left lateral position to the midline and reducing the left lateral gap of the jejunostomy.

Association of coexistence of frailty and depressive symptoms with mortality in community-dwelling older adults: Kashiwa Cohort Study.

OBJECTIVES: This study aimed to determine the longitudinal associations of the coexistence of frailty and depressive symptoms with mortality among older adults. METHODS: The study participants were community-dwelling older adults aged ≥65 years who participated in the baseline survey of the Kashiwa Cohort Study in Japan in 2012. We used Fried's frailty phenotype criteria to classify participants as non-frail (score = 0), pre-frail (1 or 2), or frail (≥3). Depressive symptoms were assessed using the GDS-15 (≥6 points). Cox proportional hazards models were used to evaluate the association of co-occurring frailty and depressive symptoms with all-cause mortality, after adjusting for sociodemographic and clinical characteristics. RESULTS: The study included 1920 participants, including 810 non-frail, 921 pre-frail, and 189 frail older adults, of which 9.0 %, 15.7 %, and 36.0 %, respectively, had depressive symptoms. Ninety-one (4.7 %) participants died during the average follow-up period of 4.8 years. Compared with non-frail participants without depressive symptoms, frail participants had greater adjusted hazard ratios for mortality: 2.47 (95 % CI, 1.16 to 5.25) for frail participants without depressive symptoms and 4.34 (95 % CI, 1.95 to 9.65) for frail participants with depressive symptoms. However, no statistically significant associations were observed in non-frail or pre-frail participants irrespective of depressive symptoms. CONCLUSION: Frail older adults with depressive symptoms have a substantially greater risk of mortality. Screening for depressive symptoms and frailty in older adults should be incorporated into health checkups and clinical practice to identify high-risk populations.

Gastric cancer with Fanconi anemia in adolescent and young adult patient diagnosed by comprehensive genome profiling using next-generation sequencing.

Recently, the results of gastric cancer treatment have improved; however, its characteristics in adolescents and young adults are not well known. We report the case of a patient with advanced gastric cancer, Fanconi anemia (FA), and primary biliary cholangitis. A 26-year-old woman visited a local physician complaining of epigastralgia. Esophagogastroduodenoscopy revealed edematous changes with poor distension and circumferential thickened folds with erosions in the gastric body. Biopsy results of the lesion specimens revealed poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography revealed gastric wall with irregular thickness, several nodules in the peritoneal cavity, and a mass lesion in the right ovary. We diagnosed the patient with T4N2M1 stage IV gastric cancer accompanied by peritoneal and ovarian metastases and initiated nivolumab with S-1 plus oxaliplatin as the first-line treatment regimen. Because of immune-related adverse events after one course of systemic treatment, the regimen was changed to ramucirumab combined with nab-paclitaxel chemotherapy as the second-line treatment. After three cycles of weekly nab-paclitaxel with ramucirumab, the decreased platelet count did not recover, and her general condition gradually deteriorated. Comprehensive genome profiling using next-generation sequencing was performed to determine the feasibility of genotype-matched therapies. Alterations in FA complementation group A (FANCA) F1263del (49.1%) and E484Q (12.3%), which encode a key component of the multiprotein FA complex, were identified. The patient died 10 months after treatment initiation. In conclusion, when treating malignancies in adolescent and young adult patients, the genomic background should be considered.

Relationship between a gum-chewing routine and oral, physical, and cognitive functions of community-dwelling older adults: A Kashiwa cohort study.

AIM: As associations between oral function and general health have been reported in community-dwelling older adults, easily implementable preventive measures are urgently required. We focused on the health benefits of gum chewing, as no studies have been carried out on the impact of gum-chewing routines on the health of older adults. This cross-sectional study aimed to determine whether the gum-chewing routine is associated with oral, physical and cognitive functions in community-dwelling older adults. METHODS: This study included 1617 community-dwelling older participants in a health survey carried out in 2021. The gum-chewing routine and weekly chewing time were assessed using a self-administered questionnaire. The outcome measures, including actual measurements of oral function, physical function, cognitive function, dietary intake and lifestyle, were evaluated using self-administered questionnaires or health surveys. RESULTS: We analyzed 1474 (mean age 76.1 ± 5.8 years, 45% women) participants for whom all data were not missing, and 14% of them had a gum-chewing routine for more than 30 min weekly. Oral functions were significantly higher in older adults with a gum-chewing routine, and there were substantially fewer participants with oral frailty (adjusted odds ratio 0.581, 95% confidence interval 0.340-0.993). Additionally, cognitive and physical functions, including grip strength, were significantly higher in the gum-chewing routine group. CONCLUSIONS: Community-dwelling older adults with a gum-chewing routine have higher oral, physical and cognitive functions. These findings indicate that a gum-chewing routine might contribute to maintaining oral function and preventing frailty. Geriatr Gerontol Int 2024; 24: 68-74.

Integrated effects of nutrition-related, physical, and social factors on frailty among community-dwelling older adults: A 7-year follow-up from the Kashiwa cohort study.

AIM: To investigate the impact of nutrition-related, physical, and social factors as well as their transitions on frailty over a 7-year follow-up period among community-dwelling older adults. METHODS: Participants were 868 non-frail older adults. Frailty was assessed using the Cardiovascular Health Study index. Nutrition-related, physical, and social factors have been defined in our previous study. Cox regression analysis was conducted to investigate the association between the three factors at baseline and new-onset frailty during a 7-year follow-up period. Furthermore, transitions in the three factors over two/three consecutive years and their association with frailty were investigated using lagged generalized estimating equations. RESULTS: The mean age was 73.8 ± 4.8 years (women, 47.0%), and the incidence of frailty was 12.5% during the 7-year follow-up period. Compared with participants who met the three factors' criteria at baseline, those who met two, one, and none showed associations with greater adjusted hazard ratios of new-onset frailty (1.73, 95% confidence interval 0.87-3.42; 2.04 [1.01-4.12]; and 5.69 [2.82-11.47]). Generalized estimating equation analysis showed that, compared with older adults who maintained all the three criteria met, those who improved the quantity of criteria met, who maintained the less than three criteria met, and who decreased the quantity of criteria met showed (marginally) significant associations with greater adjusted odds ratios of frailty (2.86 [0.88-9.31], 3.70 [1.10-12.45], and 4.75 [1.42-15.85]). CONCLUSIONS: Practicing and maintaining all three factors in daily life are crucial for frailty prevention. Future research should explore strategies to motivate behavioral modifications in these factors at the population level. Geriatr Gerontol Int 2024; 24: 162-169.

An optimal method of hydrogel spacer insertion for stereotactic body radiation therapy of prostate cancer.

PURPOSE: This study aimed to explore an ideal method for hydrogel spacer insertion by analyzing the efficacy and safety of our originally developed apex expansion method. MATERIALS AND METHODS: Overall, 100 patients with low- and intermediate-risk localized prostate cancer treated with stereotactic body radiation therapy were included. A hydrogel spacer was inserted in 64 and 36 patients using the conventional and apex expansion methods, respectively. For dosimetry, we trisected the rectum into the upper rectum, middle rectum, and lower rectum on the sagittal section of magnetic resonance imaging. We compared the dose to each part of the rectum between the two methods using dose-volume histograms. Genitourinary and gastrointestinal toxicity assessments were conducted until 3 months of follow-up. RESULTS: The whole rectal dose in the apex expansion method group was lower than that in the conventional method group, which was significant in all dose regions (V5-V35). Similarly, in the apex expansion method group, the dose to the middle rectum was lower in the low- to high-dose region (V10-V35), and the dose to the lower rectum was lower in the middle- to high-dose region (V15-35). No Grade ≥ 3 toxicity or procedure-related complications were observed. Additionally, Grade 2 genitourinary and gastrointestinal toxicities during the treatment showed no significant differences between the two methods. CONCLUSION: The apex expansion method may be safe and effective in achieving a more efficient rectal dose reduction by expanding the anterior perirectal space in the prostatic apex area.

Validity of a simple self-reported questionnaire "Eleven-Check" for screening of frailty in Japanese community-dwelling older adults: Kashiwa cohort study.

PURPOSE: Frailty was indicated to be closely related to older adults' lifestyles, especially in nutrition-related factors (such as balanced diet and oral functions), physical factors, and social factors in our previous study. Here, we developed an "Eleven-Check" (EC) questionnaire containing the aforementioned three factors. This study tested whether the EC questionnaire can estimate frailty in community-dwelling older adults. MATERIALS AND METHODS: The study sample comprised 1,523 independent older adults. The primary outcome of frailty was assessed using the Cardiovascular Health Study index. The secondary outcome of sarcopenia was assessed by the criteria of the Asian Working Group for Sarcopenia 2019. The EC questionnaire comprised 11 dichotomous factors related to nutrition-related (diet and oral functions), physical, and social factors. RESULTS: Frailty prevalence was 8.5 % (76.1 ± 5.8y, 45.1 % women). The accuracy of the EC questionnaire for frailty was optimal when the total scores of 4/5 were used as the threshold. Compared to the low-risk group (<5), the high-risk group (≥5) had a significant association between frailty with an adjusted odds ratio (aOR) of 4.68 (95 %CI, 3.10-7.05). Moreover, the high-risk group also had a significant association with sarcopenia, with an aOR of 1.82 (1.27-2.61). CONCLUSIONS: For community-dwelling older adults, the EC questionnaire was able to simply screen frailty and sarcopenia status. Further, it might raise older adults' self-awareness from a multifaceted perspective in their daily life to prevent steady decline and frailty sustainably in a community setting.

Impact of the anti-inflammatory diet on serum high-sensitivity C-Reactive protein and new-onset frailty in community-dwelling older adults: A 7-year follow-up of the Kashiwa cohort study.

AIM: Chronic inflammation is a pathophysiological cause of age-related diseases, including frailty. Although diet is a determinant of inflammation, few prospective studies have investigated its role in frailty onset. This study used the dietary inflammatory index to investigate whether a proinflammatory diet affects the incidence of frailty in a 7-year follow-up of older Japanese adults. METHODS: We enrolled community-dwelling older adults without frailty from the 2014 Kashiwa cohort study. Energy-adjusted dietary inflammatory index (E-DII) scores were calculated using a brief self-administered diet history questionnaire. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured by immunoassays. Frailty was defined as meeting three of Fried's five phenotypic criteria. Cox regression was used to analyze associations between E-DII scores and new-onset frailty after adjusting for relevant confounders. RESULTS: Overall, 95 (11.7%) of 811 participants (73.7 ± 4.8 years, women 47.3%) developed new-onset frailty during the 7-year follow-up. The baseline E-DII scores significantly correlated with log-hsCRP levels, even after adjustment (ß = 0.075, P = 0.035). The highest tertile of E-DII scores (proinflammatory diet) showed a 2.03 times (95% confidence interval, 1.22-3.36) higher risk of new-onset frailty than that associated with the lowest tertile (P = 0.006). When E-DII was calculated on the basis of anti-inflammatory food parameters only, the highest tertile showed a 2.32 times (95% confidence interval, 1.36-3.95) higher risk than that associated with the lowest tertile (P = 0.002). CONCLUSIONS: E-DII scores significantly correlated with serum hsCRP levels. High E-DII scores caused by low intake of anti-inflammatory foods are associated with frailty incidence. For community-dwelling older adults, dietary interventions that lower E-DII scores (e.g., encouraging dietary fiber intake) may help prevent frailty. Geriatr Gerontol Int 2024; 24: 189-195.

Aberrant bone marrow-derived microglia in the hypothalamus may dysregulate appetite in diabetes.

Bone marrow derived cells (BMDCs) migrate into the hypothalamus, where those cells give rise to microglia to regulate food intake. Given the fact that diabetes functionally impairs BMDCs, we hypothesized that diabetic microglia would fail to exhibit physiological function, accounting for hyperphagia in diabetes. To examine the role of BMDCs, total bone marrow cells from GFP transgenic mice were transplanted into wild type mice in which diabetes was induced by streptozotocin. We first confirmed that bone marrow transplantation could be utilized to examine BMDCs in the brain parenchyma as GFP positive cells could engraft the brain parenchyma and give rise to microglia even when the BBB was intact in the recipient mice. While diabetic mice manifested hyperphagia, BMDCs were in smaller number in the hypothalamus with less response to fasting in the brain parenchyma compared to nondiabetic mice. This finding was also confirmed by examining nondiabetic chimera mice in which BMDCs were diabetic. Those mice also exhibited less response of BMDCs in response to fasting. In conclusion, diabetic BMDCs had less response of microglia to fasting, perhaps accounting for diabetic hyperphagia.

A case of dupilumab combination therapy for exacerbation of atopic dermatitis in a patient with eosinophilic granulomatosis with polyangiitis treated with mepolizumab.

We report a 60-year-old male with eosinophilic granulomatosis with polyangiitis (EGPA) complicated with atopic dermatitis (AD). The patient was initially treated with prednisolone, cyclosporine A, and mepolizumab (MEPO). Due to worsening skin symptoms after prednisolone tapering, dupilumab (DUP) was added as an adjunctive therapy for AD confirmed by skin biopsy. The combination therapy of MEPO and DUP resulted in rapid improvement of skin symptoms, suggesting it may be an effective therapeutic option for patients with EGPA and AD. This case report emphasises the importance of a multidisciplinary approach in treating complex diseases such as EGPA and AD.

Dosimetric comparison of rectal dose-reductive techniques in intra-cavitary brachytherapy for cervical cancer: A retrospective analysis.

Purpose: Rectal complications in radiotherapy for cervical cancer can highly affect quality of life and correlate with rectal dose. Vaginal gauze packing (VP) and rectal retraction (RR) are widely used for rectal dose reduction in high-dose-rate brachytherapy. We aimed to perform a dosimetric comparison of these two methods for three-dimensional image-guided adaptive brachytherapy. Material and methods: We retrospectively examined 50 patients with cervical cancer treated with definitive radiotherapy, including intra-cavitary brachytherapy, performed with VP and RR. We extracted two fractions for each patient: one fraction with VP and the next fraction with RR, and then compared dose-volume parameters. In total, 50 fractions each were analyzed in VP and RR groups. Dose to 90% (D90) of high-risk clinical target volume (HR-CTV), and minimum dose to most exposed 2.0 cm3 of other organs at risk (D2cm3) for the rectum and bladder were determined from planning computed tomography. Results: There were no significant differences between VP and RR in D90 of HR-CTV (mean: 7.479 Gy and 7.652 Gy, respectively, p = 0.172). The D2cm3 values for the rectum (mean: 4.234 Gy vs. 4.627 Gy, p = 0.008) and bladder (mean: 5.959 Gy vs. 6.690 Gy, p < 0.001) were significantly lower with VP compared with RR. Conclusions: VP reduced the dose to the rectum and bladder when compared with RR without impairing the dose to CTV.

Oral frailty five-item checklist to predict adverse health outcomes in community-dwelling older adults: A Kashiwa cohort study.

AIM: To enable easy assessment of oral frailty; that is, an overlapping slight decline in multifaceted oral function, in any setting, we developed the oral frailty five-item checklist (OF-5), and examined its predictive validity for increased risks of physical frailty, physical disability and mortality among community-dwelling older adults. METHODS: This population-based cohort study randomly selected 2044 residents in Kashiwa, Japan, with no long-term care needs. Baseline data were collected in 2012, and follow-up data were collected in 2013, 2014, 2016, 2018 and 2021. The OF-5 includes five measures: fewer teeth, difficulty in chewing, difficulty in swallowing, dry mouth and low articulatory oral motor skills. Physical frailty was defined according to the Cardiovascular Health Study criteria. Physical disability and mortality determined from the long-term care insurance receipt database were followed for 9 years. RESULTS: Of 2031 eligible participants (mean age 73.1 ± 5.6 years; 51.1% women), 39.3% individuals with ≥2 OF-5 points had significantly increased prevalence and new-onset rate of physical frailty. After adjusting for potential confounders, oral frailty, defined as ≥2 OF-5 points, was associated with increased risks of physical disability (adjusted hazard ratio 1.40; 95% confidence interval 1.14-1.72) and mortality (adjusted hazard ratio 1.44; 95% confidence interval 1.11-1.87). The highest adjusted hazard ratios were observed in older adults with coexisting physical and oral frailty. CONCLUSIONS: The OF-5 showed strong predictive validity for physical frailty, physical disability and mortality in Japanese older adults. This assessment tool can be implemented in various settings and foster comprehensive prevention through interprofessional collaboration. Geriatr Gerontol Int 2023; 23: 651-659.

Decamethylcyclopentasiloxane affects estradiol production in female rats but not H295R cells.

Sex hormones, such as androgens and estrogens, are predominantly produced in the gonads (ovaries and testes) and adrenal cortex. Endocrine-disrupting chemicals (EDCs) are substances that mimic, block, or interfere with hormones in the endocrine systems of humans and organisms. EDCs mainly act via nuclear receptors and steroidogenesis-related enzymes. In the OECD conceptual framework for testing and assessment of EDCs, several well-known assays are used to identify the potential disruption of nuclear receptors both in vivo and in vitro, whereas the H295R steroidogenesis assay is the only assay that detects the disruption of steroidogenesis. Forskolin and prochloraz are often used as positive controls in the H295R steroidogenesis assay. Decamethylcyclopentasiloxane (D5) was suspected one of EDCs, but the effects of D5 on steroidogenesis remain unclear. To establish a short-term in vivo screening method that detects the disruption of steroidogenesis, rats in the present study were fed a diet containing forskolin, prochloraz, or D5 for 14 days. Forskolin increased plasma levels of 17ß-estradiol (E2) and testosterone as well as the mRNA level of Cyp19 in both the adrenal glands and ovaries. Prochloraz induced the loss of cyclicity in the sexual cycle and decreased plasma levels of E2 and testosterone. D5 increased E2 levels and shortened the estrous cycle in a dose-dependent manner; however, potential endocrine disruption was not detected in the H295R steroidogenesis assay. These results demonstrate the importance of comprehensively assessing the endocrine-disrupting effects of chemicals on steroidogenesis in vivo.