PGRMC2 is an intracellular haem chaperone critical for adipocyte function.

Haem is an essential prosthetic group of numerous proteins and a central signalling molecule in many physiologic processes1,2. The chemical reactivity of haem means that a network of intracellular chaperone proteins is required to avert the cytotoxic effects of free haem, but the constituents of such trafficking pathways are unknown3,4. Haem synthesis is completed in mitochondria, with ferrochelatase adding iron to protoporphyrin IX. How this vital but highly reactive metabolite is delivered from mitochondria to haemoproteins throughout the cell remains poorly defined3,4. Here we show that progesterone receptor membrane component 2 (PGRMC2) is required for delivery of labile, or signalling haem, to the nucleus. Deletion of PGMRC2 in brown fat, which has a high demand for haem, reduced labile haem in the nucleus and increased stability of the haem-responsive transcriptional repressors Rev-Erbα and BACH1. Ensuing alterations in gene expression caused severe mitochondrial defects that rendered adipose-specific PGRMC2-null mice unable to activate adaptive thermogenesis and prone to greater metabolic deterioration when fed a high-fat diet. By contrast, obese-diabetic mice treated with a small-molecule PGRMC2 activator showed substantial improvement of diabetic features. These studies uncover a role for PGRMC2 in intracellular haem transport, reveal the influence of adipose tissue haem dynamics on physiology and suggest that modulation of PGRMC2 may revert obesity-linked defects in adipocytes.

Radiotherapy for Atypical Teratoid/Rhabdoid Tumor (ATRT) on the Pediatric Proton/Photon Consortium Registry (PPCR).

PURPOSE: Atypical teratoid/rhabdoid tumors (ATRT) of the central nervous system (CNS) are rare tumors with a poor prognosis and variable use of either focal or craniospinal (CSI) radiotherapy (RT). Outcomes on the prospective Pediatric Proton/Photon Consortium Registry (PPCR) were evaluated according to RT delivered. METHODS: Pediatric patients receiving RT were prospectively enrolled on PPCR to collect initial patient, disease, and treatment factors as well as provide follow-up for patient outcomes. All ATRT patients with evaluable data were included. Kaplan-Meier analyses with log-rank p-values and cox proportional hazards regression were performed. RESULTS: The PPCR ATRT cohort includes 68 evaluable ATRT patients (median age 2.6 years, range 0.71-15.40) from 2012 to 2021. Median follow-up was 40.8 months (range 3.4-107.7). Treatment included surgery (65% initial gross total resection or GTR), chemotherapy (60% with myeloablative therapy including stem cell rescue) and RT. For patients with M0 stage (n = 60), 50 (83%) had focal RT and 10 (17%) had CSI. Among patients with M + stage (n = 8), 3 had focal RT and 5 had CSI. Four-year overall survival (OS, n = 68) was 56% with no differences observed between M0 and M + stage patients (p = 0.848). Local Control (LC) at 4 years did not show a difference for lower primary dose (50-53.9 Gy) compared to ≥ 54 Gy (73.3% vs 74.7%, p = 0.83). For patients with M0 disease, four-year OS for focal RT was 54.6% and for CSI was 60% (Hazard Ratio 1.04, p = 0.95. Four-year event free survival (EFS) among M0 patients for focal RT was 45.6% and for CSI was 60% (Hazard Ratio 0.71, p = 0.519). For all patients, the 4-year OS comparing focal RT with CSI was 54.4% vs 60% respectively (p = 0.944), and the 4-year EFS for focal RT or CSI was 42.8% vs 51.4% respectively (p = 0.610). CONCLUSION: The PPCR ATRT cohort found no differences in outcomes according to receipt of either higher primary dose or larger RT field (CSI). However, most patients were M0 and received focal RT. A lower primary dose (50.4 Gy), regardless of patient age, is appealing for further study as part of multi-modality therapy.

Targeted PMP22 TATA-box editing by CRISPR/Cas9 reduces demyelinating neuropathy of Charcot-Marie-Tooth disease type 1A in mice.

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted TATA-box of human PMP22 promoter to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multiple copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a proof-of-concept that CRISPR/Cas9-mediated targeting of TATA-box can be utilized to treat CMT1A.

The translocator protein ligands as mitochondrial functional modulators for the potential anti-Alzheimer agents.

Small molecule modulators of mitochondrial function have been attracted much attention in recent years due to their potential therapeutic applications for neurodegenerative diseases. The mitochondrial translocator protein (TSPO) is a promising target for such compounds, given its involvement in the formation of the mitochondrial permeability transition pore in response to mitochondrial stress. In this study, we performed a ligand-based pharmacophore design and virtual screening, and identified a potent hit compound, 7 (VH34) as a TSPO ligand. After validating its biological activity against amyloid-ß (Aß) induced mitochondrial dysfunction and in acute and transgenic Alzheimer's disease (AD) model mice, we developed a library of analogs, and we found two most active compounds, 31 and 44, which restored the mitochondrial membrane potential, ATP production, and cell viability under Aß-induced mitochondrial toxicity. These compounds recovered learning and memory function in acute AD model mice with improved pharmacokinetic properties.

Predictors of multidomain decline in health-related quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer.

BACKGROUND: Stereotactic body radiation therapy (SBRT) for localized prostate cancer involves high-dose-per-fraction radiation treatments. Its use is increasing, but concerns remain about treatment-related toxicity. The authors assessed the incidence and predictors of a global decline in health-related quality of life (HRQOL) after prostate SBRT. METHODS: From 2008 to 2014, 713 consecutive men with localized prostate cancer received treatment with SBRT according to a prospective institutional protocol. Expanded Prostate Cancer Index Composite (EPIC-26) HRQOL data were collected at baseline and longitudinally for 5 years. EPIC-26 is comprised of 5 domains. The primary endpoint was defined as a decline exceeding the clinically detectable threshold in ≥4 EPIC-26 domains, termed multidomain decline. RESULTS: The median age was 69 years, 46% of patients had unfavorable intermediate-risk or high-risk disease, and 20% received androgen-deprivation therapy. During 1 to 3 months and 6 to 60 months after SBRT, 8% to 15% and 10% to 11% of patients had multidomain declines, respectively. On multivariable analysis, lower baseline bowel HRQOL (odds ratio, 1.8; 95% confidence interval, 1.2-2.7; P < .01) and baseline depression (odds ratio, 5.7; 95% confidence interval, 1.3-24.3; P = .02) independently predicted for multidomain decline. Only 3% to 4% of patients had long-term multidomain declines exceeding twice the clinical threshold, and 30% of such declines appeared to be related to prostate cancer treatment or progression of disease. CONCLUSIONS: Prostate SBRT has minimal long-term impact on multidomain decline, and the majority of more significant multidomain declines appear to be unrelated to treatment. This emphasizes the importance of focusing not only on the side effects of prostate cancer treatment but also on other comorbid illnesses that contribute to overall HRQOL. Cancer 2017;123:1635-1642. © 2017 American Cancer Society.

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

PURPOSE: Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. MATERIALS AND METHODS: We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. RESULTS: Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). CONCLUSIONS: The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials.

Anatomical patterns of recurrence following biochemical relapse after post-prostatectomy salvage radiation therapy: a multi-institutional study.

OBJECTIVES: To characterise the frequency and detailed anatomical sites of failure for patients receiving post-radical prostatectomy (RP) salvage radiation therapy (SRT). PATIENTS AND METHODS: A multi-institutional retrospective study was performed on 574 men who underwent SRT between 1986 and 2013. Anatomical recurrence patterns were classified as lymphotrophic (lymph nodes only), osteotrophic (bone only), or multifocal if both were present. Isolated first failure sites were defined as sites of initial clinically detected recurrence that remained isolated for at least 3 months. RESULTS: The median follow-up after SRT was 6.8 years. The 8-year rates of local, regional, and distant failure for patients undergoing SRT were 2%, 6%, and 21%, respectively. Of the 22% men (128 of 574) who developed a clinically detectable recurrence, 17%, 50%, and 31% were lymphotrophic, osteotrophic, and multifocal, respectively. The trophic nature of metastases was prognostic for distant metastases-free survival (DMFS) and prostate cancer-specific survival (PCSS); the 10-year rates of DMFS were 18%, 5%, and 7% (P < 0.01), and PCSS were 78%, 68%, and 56% (P < 0.01), for lymphotrophic, osteotrophic, and multifocal failure patterns, respectively. CONCLUSIONS: We demonstrate that trophism for metastatic site has significant prognostic impact on PCSS in men treated with SRT. Radiographic local failure is an uncommon event after SRT when compared to historical data of patients treated with surgery monotherapy. However, distant failure remains a challenge in this patient population and warrants further therapeutic investigation.

Vessel-sparing radiation and functional anatomy-based preservation for erectile function after prostate radiotherapy.

Treatment selection for men undergoing curative treatment for prostate cancer is often a challenging decision in view of the goal of maximising cure while maintaining quality of life. Previous quality-of-life comparisons suggest that specific outcomes are associated with type of treatment (surgery vs radiation); however, the functional anatomy approach, starting with nerve-sparing prostatectomy, assumes that quality-of-life outcomes are established by anatomic preservation. Emerging applications of the functional anatomy approach for prostate radiation will ultimately allow for individualised treatments that address the normal tissue variants visible on MRI. Such approaches will encompass all essential functions affected by treatment including genitourinary, rectal, and sexual functions. In this Review, we outline the current techniques in functional anatomy-based preservation related to sexual outcomes, and outline the capacity of vessel-sparing radiotherapy to preserve sexual function in 90% of patients at the 5 year follow-up while maintaining excellent cure rates.

Independent surgical validation of the new prostate cancer grade-grouping system.

OBJECTIVE: To report the independent prognostic impact of the new prostate cancer grade-grouping system in a large external validation cohort of patients treated with radical prostatectomy (RP). PATIENTS AND METHODS: Between 1994 and 2013, 3 694 consecutive men were treated with RP at a single institution. To investigate the performance of and validate the grade-grouping system, biochemical recurrence-free survival (bRFS) rates were assessed using Kaplan-Meier tests, Cox-regression modelling, and discriminatory comparison analyses. Separate analyses were performed based on biopsy and RP grade. RESULTS: The median follow-up was 52.7 months. The 5-year actuarial bRFS for biopsy grade groups 1-5 were 94.2%, 89.2%, 73.1%, 63.1%, and 54.7%, respectively (P < 0.001). Similarly, the 5-year actuarial bRFS based on RP grade groups was 96.1%, 93.0%, 74.0%, 64.4%, and 49.9% for grade groups 1-5, respectively (P < 0.001). The adjusted hazard ratios for bRFS relative to biopsy grade group 1 were 1.98, 4.20, 5.57, and 9.32 for groups 2, 3, 4, and 5, respectively (P < 0.001), and for RP grade groups were 2.09, 5.27, 5.86, and 10.42 (P < 0.001). The five-grade-group system had a higher prognostic discrimination compared with the commonly used three-tier system (Gleason score 6 vs 7 vs 8-10). CONCLUSIONS: In an independent surgical cohort, we have validated the prognostic benefit of the new prostate cancer grade-grouping system for bRFS, and shown that the benefit is maintained after adjusting for important clinicopathological variables. The greater predictive accuracy of the new system will improve risk stratification in the clinical setting and aid in patient counselling.

Predictors of a Successful Outcome Following a Thoracic Erector Spinae Plane Block for Cervical Radiculopathy.

BACKGROUND: The erector spinae plane block (ESPB) is an interfascial plane block for managing neuropathic thoracic pain. Although the ESPB is applied widely in various clinical situations, no studies have evaluated the association between the analgesic outcomes of the ESPB and the numerical changes in the perfusion index (PI) and PI ratio. OBJECTIVES: The purpose of this study is to investigate the association between the clinical response following ESPB and other possible factors, including changes in the PI and PI ratio. STUDY DESIGN: A prospective, nonrandomized, and open-label study. SETTING: The pain clinic of a tertiary university hospital. METHODS: This study included 92 patients with neck or arm pain who received T2 ESPB using 20 mL of 0.2% ropivacaine. To aid in the prediction of clinical outcomes, the PI was measured at the blocked side for 30 minutes as soon as the ESPB was finished. Various demographic data were also analyzed to predict the clinical outcomes. RESULTS: Among 92 patients, 59 patients (64%) showed successful treatment outcomes (> 50% reduction in the numerical rating scale score or > 30% reduction in the neck disability index). The baseline PI of the responders was statistically higher than the nonresponders' (P < 0.05). Also, the responders' PI demonstrated statistically higher values than the nonresponders' at the time points of 4, 6, and 8 minutes after the ESPB. Multivariate logistic regression analysis revealed that a higher baseline PI (OR, 1.91; 95% CI, 1.27-2.86; P = 0.002) was an independent factor associated with a successful outcome. LIMITATIONS: Only a small number of patients with nonspinal diseases were included, except for those who had cervical radiculopathy. Therefore, it is hard to conclude that thoracic ESPB has any therapeutic benefits to patients with nonspinal diseases such as complex regional pain syndrome, adhesive capsulitis, or post-thoracotomy pain syndrome. CONCLUSION: A successful outcome at 4 weeks after T2 ESPB was achieved in 64% of patients with cervical radiculopathy. A higher baseline PI value was an independent factor associated with a successful response to T2 ESPB.

Sympatholytic Effect of the High Thoracic Erector Spinae Plane Block.

BACKGROUND: The erector spinae plane block (ESPB), which was introduced for the management of thoracic pain, is a technically easy and relatively noninvasive ultrasound (ULSD)-guided technique. Although the ESPB is used widely in variable clinical situations, its sympatholytic effect has never been studied. OBJECTIVES: The purpose of this study is to demonstrate the sympatholytic effect of the high thoracic ESPB by comparing the blocked and unblocked sides of patients' upper extremities, using the changes in the perfusion index (PI). STUDY DESIGN: Prospective, single-group, and open-label study. SETTING: The study was carried out in the pain clinic of a tertiary university hospital. METHODS: This study included 47 patients with upper extremity pain and various diseases who received T2 or T3 ESPBs using 20 mL of 0.2% ropivacaine. For the evaluation of the sympatholytic effect, measurements were taken on the numeric rating scale (NRS), the neck disability index (NDI), and the PI. RESULTS: The PIs of the blocked sides demonstrated significant increases at 10, 20, and 30 minutes compared to the PIs of the baseline and unblocked sides (P < 0.001). The PI ratio at 10 minutes was 2.74 ± 1.65, which was the highest value during the measurement period. Until 30 minutes after the ESPB, the PI ratio was significantly higher in the blocked side than in the unblocked side. During the study period, significant reductions in NRS and NDI scores were found irrespective of disease entity. LIMITATION: The period of PI measurement was only 30 minutes, so we could not determine the time point when the PI returned to the baseline value. CONCLUSION: The high thoracic ESPB was effective in relieving upper extremity pain in diverse disease entities, and the PIs of patients' blocked sides demonstrated significant increases over the baseline value and contralateral unblocked sides.

FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells.

Little is known about whether autophagic mechanisms are active in hematopoietic stem cells (HSCs) or how they are regulated. FIP200 (200-kDa FAK-family interacting protein) plays important roles in mammalian autophagy and other cellular functions, but its role in hematopoietic cells has not been examined. Here we show that conditional deletion of FIP200 in hematopoietic cells leads to perinatal lethality and severe anemia. FIP200 was cell-autonomously required for the maintenance and function of fetal HSCs. FIP200-deficient HSC were unable to reconstitute lethally irradiated recipients. FIP200 ablation did not result in increased HSC apoptosis, but it did increase the rate of HSC proliferation. Consistent with an essential role for FIP200 in autophagy, FIP200-null fetal HSCs exhibited both increased mitochondrial mass and reactive oxygen species. These data identify FIP200 as a key intrinsic regulator of fetal HSCs and implicate a potential role for autophagy in the maintenance of fetal hematopoiesis and HSCs.

Red blood cell preservation by droplet freezing with polyvinylpyrrolidone or sucrose-dextrose and by bulk freezing with glycerol.

BACKGROUND: Red blood cell (RBC) preservation is essential to transfusion medicine. Many blood group reference laboratories need a method to preserve rare blood samples for serologic testing at a later date. This study offers a comparison of three common cryoprotective agents and protocols used today: bulk preservation with glycerol and droplet freezing with sucrose-dextrose (S+D) or polyvinylpyrrolidone (PVP). STUDY DESIGN AND METHODS: Human blood from 14 volunteers was collected and frozen at set intervals over 2 weeks with PVP, S+D, or glycerol. The frozen RBCs were later thawed and the percentage of surviving RBCs was determined. Detailed protocols and an instructional video are supplied. RESULTS: Over a 2-week period, RBCs preserved with glycerol and thawed with a widely used protocol showed a recovery of 41 ± 16% (mean ± standard deviation) while those thawed with a modified glycerol protocol showed a recovery of 76 ± 8%. RBCs preserved by droplet freezing with S+D showed a recovery of 56 ± 11% while those preserved by droplet freezing with PVP showed a recovery of 85 ± 6%. Recovery values were similar with ethylenediaminetetraacetic acid or heparin anticoagulants, differing freezing rates, and varying droplet volumes. CONCLUSION: Droplet freezing with PVP offered the greatest recovery. While bulk freezing with glycerol can also be effective, droplet freezing may be a more convenient method overall. It requires less effort to thaw, needs much less storage room, and allows blood group laboratories to be frugal with thawing rare samples.

Congenital cervical bronchogenic cyst in a calf.

The present report describes an extrathoracic bronchogenic cyst in a 30-day-old female calf. Histologically, the cyst wall was lined by a layer of ciliated pseudostratified columnar epithelium with peripheral arrangement of cartilage, glands, and smooth muscle fascicles. The mass was successfully removed by simple surgical excision.

Development of a Comprehensive, Contour-Based, Peer Review Workflow at a Community Proton Center.

PURPOSE: Quality assurance and continuing quality improvement are integral parts of any radiation oncology practice. With increasingly conformal radiation treatments, it has become critical to focus on every slice of the target contour to ensure adequate tumor coverage and optimal normal tissue sparing. Proton therapy centers open internationally with increasing frequency, and radiation oncologists with varying degrees of subspecialization apply proton therapy in daily practice. Precise treatment with proton therapy allows us to limit toxicity but requires in-depth knowledge of the unique properties of proton beam delivery. To address this need at our proton therapy center, we developed a comprehensive peer review program to help improve the quality of care that we were providing for our patients. MATERIALS AND METHODS: We implemented a policy of comprehensive peer review for all patients treated at our community proton facility starting in January 2013. Peer review begins at the time of referral with prospective cases being reviewed for appropriateness for proton therapy at daily rounds. There is then biweekly review of target contouring and treatment plans. RESULTS: During a 6-month period from June 2013 to November 2013, a total of 223 new patients were treated. Documentation of peer review at chart rounds was completed for 222 of the 223 patients (99.6%). An average of 10.7 cases were reviewed in each biweekly chart rounds session, with a total of 560 case presentations. The average time required for contour review was 145 seconds (±71 seconds) and plan review was 120 seconds (±64 seconds). Modifications were suggested for 21 patients (7.9%) during contour review and for 19 patients (6.4%) during treatment plan review. An average of 4 physicians were present at each session. CONCLUSIONS: We demonstrated that the implementation of a comprehensive, prospective peer review program is feasible in the community setting. This article can serve as a framework for future quality assurance programs.

Development of tau-directed small molecule modulators for Alzheimer's disease: a recent patent review (2014-2018).

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by memory loss and cognitive impairment. As this disease is becoming a serious global health issue, development of disease modifying therapeutics is urgently required. AD is characterized by deposits of two protein, amyloid ß and tau. Although amyloid ß-based therapeutics have been extensively investigated so far, tau has also received great attention as one of promising molecular targets for AD. In this review, a variety of tau-directed strategies to rescue tau-mediated neurotoxicity will be reviewed especially focusing on small molecules. Subsequently, recent patents published from 2014 to 2018 that integrate efforts to develop tau-directed small molecules for the treatment of AD will be reviewed.

Volumetric 18 F-FDG-PET parameters as predictors of locoregional failure in low-risk HPV-related oropharyngeal cancer after definitive chemoradiation therapy.

BACKGROUND: We sought to investigate the prognostic value of volumetric positron emission tomography (PET) parameters in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and a ≤10 pack-year smoking history treated with chemoradiation. METHODS: A total of 142 patients were included. Maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of the primary tumor, involved regional lymph nodes, and total lesion were calculated. Cox proportional hazard modeling was used to evaluate associations of clinical and PET parameters with locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: On univariate analysis, volumetric PET parameters were significantly associated with all endpoints, and 8th edition American Joint Committee on Cancer/Union Internationale Contre le Cancer staging was significantly associated with DMFS and OS. On multivariate analysis, total lesion TLG was significantly associated with LRFFS, while staging was most significantly prognostic for DMFS and OS. CONCLUSION: Volumetric PET parameters are uniquely prognostic of LRFFS in low-risk HPV-related OPSCC and may be useful for directing de-intensification strategies.

Risk of dermal and inhalation exposure to chlorantraniliprole assessed by using whole-body dosimetry in Korea.

BACKGROUND: We determined the characteristics and evaluated associated risks of sprayed pesticide exposure among workers cultivating Korean cabbage. The test pesticide, a mixture of 3% chlorantraniliprole and 4% indoxacarb wettable granules diluted 2000 times, was sprayed on Korean cabbage within a 3000 m2 area in Goesan, Korea. Dermal exposures were measured using a whole-body dosimetry method. RESULTS: Exposure to chlorantraniliprole was observed among ten individuals, ranging from 140.4 to 4234.0 µg person-1 . The legs were the most prominent exposure area (86.35%), with the face being the least exposed (0.06%). Exposure risk was assessed by calculating the margin of safety (MOS) on the exposure amount for each body part. The MOS based on dermal and inhalation exposure doses ranged from 59 to 1765. CONCLUSION: Exposure was the greatest for the legs, probably as a result of the low height of the crop and the use of a long-wand sprayer. An MOS value >1 indicates a low risk for applicators using this method of application. However, with tall crops, exposure level and MOS values can vary widely, as MOS increases or decreases based on exposure dose. Therefore, future research is needed to better understand appropriate safety precautions when working with potent pesticides. © 2018 Society of Chemical Industry.

Dissipation, persistence, and risk assessment of fluxapyroxad and penthiopyrad residues in perilla leaf (Perilla frutescens var. japonica Hara).

The objective of this study was to determine the residual characteristics and to calculate the persistence of the fungicides fluxapyroxad (15.3% suspension concentrate) and penthiopyrad (20% emulsifiable concentrate) on the leaves of greenhouse-cultivated perilla (Perilla frutescens var. japonica Hara). Fluxapyroxad was diluted 2,000-fold and penthiopyrad was diluted 4,000-fold. Each solution was sprayed 3 times onto crops at 7-d intervals before harvest. Leaf samples were collected at 3 h (0 d), 1, 3, 5 and 7 d after the third and final treatment. The recovery ranges of fluxapyroxad and penthiopyrad and their metabolites were 74.2%-104.1%. Pesticide residue analyses indicated that fluxapyroxad and penthiopyrad residues in perilla leaves dissipated over time. The persistence of fluxapyroxad and penthiopyrad residues 7 d after the final spray were 50.0% ± 4.9% and 44.2% ± 2.8% of those measured 3 h (0 d) after the final spray, respectively. The percent acceptable daily intake (%ADI)-which was assessed according to the daily food intake by Koreans according to age-was < 7.3%. Therefore, it was determined that the health risk was low. The perception that residual pesticides are present in large amounts in perilla leaf has led to consumer concern. However, in this study, the amounts of pesticide in perilla leaf decreased over time. Although it has been hypothesized that the risk of pesticide intake would be higher in younger children, the results actually suggest the opposite. Therefore, the pesticides in question are considered to be safe for use on perilla leaves.