Identifying genetic variants underlying medication-induced osteonecrosis of the jaw in cancer and osteoporosis: a case control study

Background Bisphosphonate-induced osteonecrosis of the jaw (BRONJ) presents with a typical pattern of jaw necrosis in patients who have been prescribed bisphosphonates (BPs) and other antiangiogenetic drugs to treat osteoporosis or bone-related complications of cancer. Methods This study divided 38 patients with BRONJ into two groups according to the prescribing causes: cancer (n = 13) and osteoporosis (n = 25), and underwent whole exome sequencing and compared them with normal controls (n = 90). To identify candidate genes and variants, we conducted three analyses: a traditional genetic model, gene-wise variant score burden, and rare-variant analysis methods. Results The stop-gain mutation (rs117889746) of the PZP gene in the BRONJ cancer group was significantly identified in the additive trend model analysis. In the cancer group, ARIDS, HEBP1, LTBP1, and PLVAP were identified as candidate genes. In the osteoporosis group, VEGFA, DFFA, and FAM193A genes showed a significant association. No significant genes were identified in the rare-variant analysis pipeline. Biologically accountable functions related to BRONJ occurrence-angiogenesis-related signaling (VEGFA and PLVAP genes), TGF-β signaling (LTBP1 and PZP genes), heme toxicity (HEBP1) and osteoblast maturation (ARIDS)-were shown in candidate genes. Conclusion This study showed that the candidate causative genes contributing to the development of BRONJ differ according to the BP dose and background disease.This work was supported by the Education and Research Encouragement Fund of Seoul National University Hospital and the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF2018R1D1A1A02086109). There are no conficts of interest to declare

Diel cell cycle analysis of Heterosigma akashiwo (Raphidophyceae) with special reference to vertical migration behavior

The marine alga, Heterosigmaakashiwo(Raphidophyceae), is known to frequentlyform blooms in temperate coastal waters throughoutthe world (Horner et al. 1997; Smayda 1998; Taylorand Haigh 1993; Taylor and Horner 1994). H.akashiwo populations usually develop rapidly in earlysummer (Imai 2000; Shikata et al. 2007), formingdense blooms in the upper water column at or near thesurface (Handy et al. 2005; Honjo 1993; Yamochi andAbe 1984). Its blooms can cause massive fish killsthrough the production of chemicals such asneurotoxins, cardiotoxins, and reactive oxygen (Endoet al. 1992; Khan et al. 1997). In addition to thesignificant impacts to fish populations, algal bloomscan cause a decrease in plankton biodiversity and aresometimes accompanied by low oxygen in deeperwater (Tsutsumi 2006) which may kill shellfish andother invertebrates. Given these potential impacts, abetter understanding of the conditions leading to analgal bloom, and the bloom process itself, areimportant in helping to protect coastal ecosystems.The accumulation of algae on the surfacewater is caused by biological processes such as growthand vertical migration (Bearon et al. 2006) and/orphysical processes such as wind-driven advection (Hill1991). These events should be considered separately inthe analysis of the bloom-development process. Sincecells of H. akashiwo can accumulate in “nutrientdepleted”surface waters during the daytime and movedownward to “nutrient-rich” bottom waters at night(Watanabe et al. 1983; Watanabe et al. 1988), growthrate measurement for this species is quite difficultwhen employing in situ incubation experiments usingbottles

Biochemical Compositions and Biological Activities of Extracts from 3 Species of Korean Pine Needles

Abstract Crude extracts of pine needles have long been used as a health-food and for cosmetics. In this study, we determined the biochemical composition and biological activities of extracts from three pine species: red pine (RP, Pinus densiflora S et Z), Keumkang pine (KP, Pinus densiflora for. erecta) and sea pine (SP, Pinus thunbergii). The SP extract had the highest levels of moisture, ash, crude protein, and lipids based on the dry weight. The SP extract also had the highest level of polyunsaturated fatty acids (PUFAs). The SP extract had much more β-pinene, β-caryophyllene, and germacrene-D than extracts from the other species. Total phenolic content was the highest in the 100% ethanol extract of SP, and the 50% ethanol extract of SP had the highest DPPH radical scavenging activity. The SP extract had the greatest antimicrobial effect. These results indicate that SP has the greatest potential as a natural antioxidant resource and raw material for cosmetic-goods

South Korean geriatrics on Beers Criteria medications at risk of adverse drug events.

The Beers Criteria released by the American Geriatrics Society includes a list of drugs to avoid in the geriatric population and is frequently used as a safety resource in geriatric pharmacotherapy.To evaluate the exposure of South Korean geriatrics to potentially inappropriate medications according to the Beers Criteria and the risk of adverse events from these medications.This study included medications recommended to be avoided in patients 65 years or older regardless of concomitant drug therapy or disease. The exposure of South Korean geriatrics to each of the study medications were examined using health claims data of 2011. The number of South Korean geriatrics at risk of experiencing adverse drug events from the study medications were estimated by multiplying the number of patients exposed to the medication in 2011 and the incident rate of the event obtained from literature sources.This study examined 166,822 geriatrics for Beers Criteria medication exposure and adverse drug event risk. The most prevalent Beers Criteria medication prescribed in South Korean geriatrics >1 day was chlorpheniramine (53.9%) and the adverse drug event with the highest number of this geriatric population at risk of was amitriptyline related dry mouth (4.9%). The proportion of South Korean geriatrics on chronic Beers Criteria medications >1 day at risk of adverse drug events from these medications was significantly higher than in US geriatrics (0.005 vs. 0.001, 2-way ANOVA post hoc pairwise t-test P<0.0001).In 2011, over half of South Korean geriatrics was exposed to medications recommended to be avoided in geriatrics and their adverse drug event risk warrants close monitoring of their occurrence

Genomics-based Sensitive and Specific Novel Primers for Simultaneous Detection of Burkholderia glumae and Burkholderia gladioli in Rice Seeds

Panicle blight and seed rot disease caused mainly by Burkholderia glumae and Burkholderia gladioli is threatening rice cultivation worldwide. The bacteria have been reported as seed-borne pathogens from rice. Accurate detection of both pathogens on the seeds is very important for limiting the disease dissemination. Novel primer pairs targeting specific molecular markers were developed for the robust detection of B. glumae and B. gladioli. The designed primers were specific in detecting the target species with no apparent cross-reactions with other related Burkholderia species at the expected product size. Both primer pairs displayed a high degree of sensitivity for detection of B. glumae and B. gladioli separately in monoplex PCR or simultaneously in duplex PCR from both extracted gDNA and directly preheated bacterial cell suspensions. Limit of detection was as low as 0.1 ng of gDNA of both species and 3.86 × 10² cells for B. glumae and 5.85 × 10² cells for B. gladioli. On inoculated rice seeds, the designed primers could separately or simultaneously detect B. glumae and B. gladioli with a detection limit as low as 1.86 × 10³ cells per rice seed for B. glumae and 1.04 × 10⁴ cells per rice seed of B. gladioli. The novel primers maybe valuable as a more sensitive, specific, and robust tool for the efficient simultaneous detection of B. glumae and B. gladioli on rice seeds, which is important in combating rice panicle blight and seed rot by early detection and confirmation of the dissemination of pathogen-free rice seeds

Overall workflow of the study.

<p><i>AGS</i> American Geriatrics Society; <i>ADE</i> adverse drug event, <i>BCM</i> Beers Criteria medication.</p

Mean (SD) proportion of South Koreans on Beers Criteria medications >1 day and US geriatrics at risk of Beers Criteria medication related adverse drug events grouped by system organ class.

<p>The SOCs were <i>A</i> blood and lymphatic system disorders (Beers Criteria medication-ADE pairs, n = 0 for South Korea, n = 2 for US); <i>B</i> cardiac disorders (n = 5 for South Korea, n = 15 for US); <i>C</i> eye disorders (n = 1 for South Korea, n = 1 for US); <i>D</i> gastrointestinal disorders (n = 13 for South Korea, n = 30 for US); <i>E</i> general disorders and administration site conditions (n = 6 for South Korea, n = 15 for US); <i>F</i> hepatobiliary disorders (n = 1 for South Korea, n = 0 for US); <i>G</i> injury, poisoning and procedural complications (n = 2 for South Korea, n = 3 for US); <i>H</i> investigations (n = 5 for South Korea, n = 2 for US); <i>I</i> metabolism and nutrition disorders (n = 1 for South Korea, n = 6 for US); <i>J</i> musculoskeletal and connective tissue disorders (n = 1 for South Korea, n = 3 for US); <i>K</i> nervous system disorders (n = 18 for South Korea, n = 33 for US); <i>L</i> psychiatric disorders (n = 11 for South Korea, n = 22 for US); <i>M</i> renal and urinary disorders (n = 1 for South Korea, n = 4 for US); <i>N</i> reproductive system and breast disorders (n = 1 for South Korea, n = 1 for US); <i>O</i> respiratory, thoracic and mediastinal disorders (n = 0 for South Korea, n = 1 for US); <i>P</i> skin and subcutaneous tissue disorders (n = 3 for South Korea, n = 2 for US); <i>Q</i> surgical and medical procedures (n = 0 for South Korea, n = 2 for US); <i>R</i> vascular disorders (n = 4 for South Korea, n = 9 for US); <i>S</i> composite of multiple SOCs (n = 7 for South Korea, n = 8 for US). <i>ADE</i> adverse drug event; <i>SOC</i> system organ class; <i>SD</i> standard deviation.</p

Mean (SD) proportion of South Koreans on Beers Criteria medications >1 day and ≤1 day at risk of Beers Criteria medication related adverse drug events grouped by system organ class.

<p>The population number used as the denominator to obtain the proportion in the y-axis was the number of South Korean geriatrics 65 years of age or older, n = 166,822. The SOCs were <i>A</i> cardiac disorders (Beers Criteria medication-ADE pairs, n = 5); <i>B</i> eye disorders (n = 1); <i>C</i> gastrointestinal disorders (n = 13); <i>D</i> general disorders and administration site conditions (n = 6); <i>E</i> hepatobiliary disorders (n = 1); <i>F</i> injury, poisoning and procedural complications (n = 2); <i>G</i> investigations (n = 5); <i>H</i> metabolism and nutrition disorders (n = 1); <i>I</i> musculoskeletal and connective tissue disorders (n = 1); <i>J</i> nervous system disorders (n = 18); <i>K</i> psychiatric disorders (n = 11); <i>L</i> renal and urinary disorders (n = 1); <i>M</i> reproductive system and breast disorders (n = 1); <i>N</i> skin and subcutaneous tissue disorders (n = 3); <i>O</i> vascular disorders (n = 4); <i>P</i> composite of multiple SOCs (n = 7). <i>ADE</i> adverse drug event; <i>BCM</i> Beers Criteria medication; <i>SOC</i> system organ class; <i>SD</i> standard deviation.</p