Search

Kallmann syndrome, a congenital disorder of idiopathic hypogonadotropic hypogonadism associated with anosmia, results in infertility because of anovulation. Assisted reproductive technology (ART) is considered when optimal ovulation induction therapy is difficult or when several cycles of ovulation induction therapy do not result in pregnancy. However, evidence is lacking regarding the optimal ART treatment for Kallmann syndrome. We report the case of a 33-year-old woman who successfully achieved pregnancy and delivery after ART treatment. At 29 years old, she was diagnosed with Kallmann syndrome due to hypothalamic amenorrhea and anosmia. At 33 years old, she revisited the hospital, desiring a child after one year of infertility. Due to anovulation, she was treated with gonadotropin therapy, but controlling follicular development was difficult, and thus ART treatment was initiated. The controlled ovarian stimulation (COS) protocol for ART treatment employed gonadotropins, recombinant follicular stimulating hormone/human menopausal gonadotropin plus human chorionic gonadotropin, to promote follicular growth. Four oocytes were retrieved, and two cleaved embryos were vitrified and cryopreserved. After vitrified-warmed embryo transfer of a morula stage embryo in a hormone replacement cycle, pregnancy was achieved but resulted in a miscarriage. A second oocyte retrieval was performed under the same COS; four oocytes were retrieved, and two cleaved embryos were vitrified and cryopreserved. Further, a pregnancy was achieved through the vitrified warmed embryo transfer. At 40 weeks and 6 days of gestation, a baby boy weighing 3,344 g with an Apgar score of 7/8 was delivered vaginally. The mother's postpartum course and neonate were free from adverse events. For women with Kallmann syndrome, ART treatment and selective embryo cryopreservation may be a reasonable and safe option.

Background: Epithelial ovarian cancer is the most frequent gynecologic malignancy; it has a poor prognosis and often occurs bilaterally. Most cases of synchronous bilateral ovarian cancer (SBOC) are metastases from the other ovary, while bilateral primary ovarian cancer is rare., Case Presentation: The patient was a 47-year-old Japanese woman with a complaint of abdominal pain for 1 month. Imaging results revealed bilateral ovarian tumors with suspicion of malignancy. The patient underwent a laparotomy with total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy, and resection of suspected dissemination in the peritoneum. Histopathological and immunohistochemical studies showed that the right ovarian tumor was an endometrioid carcinoma (G2) and had no association with endometriotic lesions. However, the left ovarian tumor was a high-grade serous carcinoma (HGSC). The final staging was stage 1 right endometrioid carcinoma and stage IIb left HGSC. Six courses of adjuvant chemotherapy with paclitaxel, docetaxel, and carboplatin were administered. The patient showed no signs of recurrence 24 months postoperatively., Conclusions: To the best of our knowledge, the combination of histological types in this case may be the first report of primary bilateral ovarian cancer. In SBOC, it is important to differentiate the subtypes of histology using immunostaining, in addition to morphopathology., (© 2022. The Author(s).)

COVID-19 has caused disruptions in health care, in particular cancer screenings. The primary aim of our work was to evaluate the degree to which populations were accepting of home-based screenings for colorectal cancer (CRC) and cervical cancer (primary HPV testing). Three groups of adults having distinct health burdens which may affect acceptance of home-based cancer screening were identified through outpatient electronic medical records as follows as either having survived a COVID hospitalization, having been positive for non-COVID respiratory illness or having type 2 diabetes. 132 respondents (58% female) completed an online survey with hypothetical cases about their acceptance of home-based CRC or cervical cancer screening. Among females, urine and vaginal screening for primary HPV testing was acceptable to 64% and 59%, respectively. Among both males and females, CRC home screening with fecal immunochemical test (FIT) or Cologuard was acceptable to 60% of the respondents. When adjusting for education, women with a positive attitude toward home-based urine /vaginal screening were 49 times and 23 times more likely to have a positive attitude toward CRC screening (aOR=48.7 (95% CI: 7.1, 337) and aOR=23.2 (95% CI: 3.8, 142), respectively). This report indicates that home-based cancer screens for CRC and primary HPV testing are acceptable to men and women and may allow for greater compliance with screening in the future., Competing Interests: Authors report none., (2021 Annals of Family Medicine, Inc.)

Background: This study describes medical malpractice claims from a large academic family medicine department over 20 years. The intent of this investigation is to analyze trends within the department, seeking to better understand how to improve the quality of patient care., Study Design: The Office of Patient Relations and Clinical Risk (PRCR) at University of Michigan Health maintains a centralized database of family medicine malpractice claims dating back to 1987. Records from 2000 to 2020 were requested from this database and received in a deidentified manner to protect patient confidentiality, and as such this study was exempt from IRB review. A total of 55 claims occurred during this time period. These claims were then analyzed in both qualitative and quantitative terms., Results: Of the 55 claims, 87.3% involved adult patients; 76.5% of the claims occurred in the outpatient setting; 98.1% of the claims involved attending physicians and 26.9% involved resident physicians; 54.5% of the claims were closed without payment and 43.6% of the claims were settled. The average settled claim amount was $742,110.50 which dropped to $160,838.59 after excluding obstetric claims. In addition, 61.8% of the claims were related to diagnosis related allegations and 16.4% of the claims involved treatment related allegations. Primarily involving allegations of missed or delayed diagnoses of cancer, 29.1% of the claims were cancer related. While 79.2% of settled claims did not meet standard of care, 83.3% of the claims closed without payment did meet standard of care., Conclusions: Most claims involved adult patients, occurred in the outpatient setting, and involved diagnosis related allegations. Although representing a minority of the claims, obstetric claims made up most of the total settlement amount. Missed or delayed diagnoses of cancer were a common cause for claims, reinforcing the important role that primary care physicians have in supervising and administering preventative health care to patients. This study also emphasizes the value of peer review committees to help inform medical-legal consultants as evidenced by the high correlation between standard of care determination and final claims outcomes., Competing Interests: Competing interest: There is no conflicting or competing interests., (© Copyright 2022 by the American Board of Family Medicine.)

Background: We sought to assess the prognostic utility of 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with metastatic castrate resistant prostate cancer (mCRPC) undergoing primary docetaxel chemotherapy., Methods: We performed a single institution retrospective analysis of 77 mCRPC patients who were treated with 6 cycles of docetaxel chemotherapy, and who also underwent 11C-choline PET/CT scans at baseline (before chemotherapy), mid-course (after 3 cycles), and posttherapy (after 6 cycles). We evaluated treatment response based on percent change in blood pool-corrected maximum standardized uptake value (SUVmax) of the target lesion on PET/CT, as well as percent change in serum prostate specific antigen (PSA). Logistic regression analysis was used to identify factors associated with complete treatment response. Progression free survival (PFS) analysis was performed using log-rank test and shown on Kaplan-Meier plot., Results: Percent change in blood pool-corrected SUVmax on mid-course scan was a significant predictor of complete response (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96-0.99, p = .0003), whereas percent change in PSA was not (OR: 0.99, 95% CI: 0.99-1.01, p = .6025). 57 of 77 patients (74%) achieved ≥20% reduction in blood pool-corrected SUVmax on mid-course; these patients were 3.6 times more likely to achieve complete response after full 6 cycles of docetaxel chemotherapy, compared to patients with <20% reduction in blood pool-corrected SUVmax (OR: 3.56, 95% CI: 1.04-16.52, p = .0420). Median PFS in the complete response group was 35.1 months (95% CI: 26.0-52.7 months), compared to 9.4 months (95% CI: 6.9-13.0 months) in the incomplete response group (p = .0005)., Conclusions: Our study showed that mid-course and posttherapy 11C-choline PET/CT evaluation for mCRPC patients undergoing primary docetaxel chemotherapy can predict full course treatment response and PFS, respectively. 11C-choline PET/CT imaging may provide valuable prognostic information to guide treatment choices for patients with mCRPC., (© 2021 Wiley Periodicals LLC.)

The purpose of this study is to clarify the practices of Certified Nurses in Dementia Nursing during the 2019 Coronavirus pandemic (COVID-19) from two perspectives: 1) protecting elderly people with dementia from contracting the virus and 2) providing basic care for dementia to ensure the maintenance of cognitive function and comfort and safety. A self-constructed questionnaire was used to survey 386 Certified Nurses in Dementia Nursing working at hospitals in 23 prefectures where more than 30% of the population is 65 years old and over about their nursing practices and the measures they were taking during the COVID-19 pandemic. It was clarified that the certified nurses devised ways to prevent infection without undue imposition on people with dementia, and that they facilitated interactions with people and created a comfortable environment while paying attention to the prevention of infection.

Objective: To identify the incidence of venous thromboembolism (VTE) risk factors, postoperative VTE, and to assess the morbidity of perioperative pharmacologic VTE prophylaxis in men undergoing inflatable penile prosthesis (IPP) surgery., Methods: We retrospectively reviewed 215 patients undergoing IPP surgery between July 2017 and June 2019. Univariate and multivariate statistical analyzes were performed to assess pre-operative Caprini risk score and compare post-operative day 0 scrotal drain output, scrotal hematoma formation, and VTE in men who received subcutaneous heparin (SqH) vs those who did not receive SqH., Results: Of 215 IPP patients, 84% were classified as high or highest risk for VTE utilizing the Caprini risk score. A total of 119 (55%) received perioperative SqH with or without additional anti-thrombotics. Post-operative day 0 scrotal drain output was higher in those who received SqH compared to those who did not receive SqH, 99.9 mL vs 75.6 mL, respectively (P = .001). Minor scrotal hematomas occurred in similar rates in patients who received perioperative SqH vs those who did not, 3.8% vs 6.3%, respectively (P = .38). Similar results were found on subgroup analysis when eliminating patients who received SqH concurrently with other anti-thrombotics. The overall rate of postoperative VTE was 0.9%. No post-operative infections occurred., Conclusion: Patients undergoing IPP surgery are at elevated risk for VTE. To our knowledge, this is the first study showing SqH use in the perioperative IPP surgery setting is safe when used in conjunction with a scrotal drain. Preoperative VTE risk stratification may be performed and can be used to guide clinical decision making regarding pharmacologic prophylaxis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Pregnancy in a rudimentary horn is an extremely rare type of ectopic pregnancy. A rudimentary uterine horn pregnancy is associated with a risk of spontaneous rupture and bleeding during surgery due to the increased uterine blood flow. Recent advances in imaging modalities have enabled laparoscopic surgery to be performed in cases without rupture in the early stages of pregnancy. However, there are few reports of successful pregnancies and deliveries after treatment of rudimentary horn pregnancies. We report the successful management of a case of non-communicating rudimentary horn pregnancy by local injection of methotrexate followed by complete laparoscopic excision along with a review of the literature., Case Presentation: The patient was a 29-year-old Japanese woman, gravida 2, nullipara. She was diagnosed with a left unicornuate uterus with a right non-communicating rudimentary horn on hysterosalpingography and magnetic resonance imaging. A gestational sac with a heartbeat was observed in the right rudimentary uterine horn at 6 weeks of gestation. A diagnosis of ectopic pregnancy in a non-communicating rudimentary horn was made. Color Doppler detected multiple blood flow signals around the gestational sac, which were clearly increased compared to the left unicornuate uterus. Her serum human chorionic gonadotropin level was 104,619 mIU/ml. A 100 mg methotrexate injection into the gestational sac was administered, and laparoscopic surgery was performed on day 48 after the methotrexate treatment. The right rudimentary horn and fallopian tube were successfully excised with minimal bleeding. A spontaneous normal pregnancy was established 6 months after the surgery. The pregnancy was uneventful, and a baby girl was born by elective cesarean section at 38w0d., Conclusion: Combined local methotrexate injection and laparoscopic surgery are safe treatment options for patients with a unicornuate uterus with a non-communicating rudimentary horn pregnancy., (© 2021. The Author(s).)

The COVID-19 pandemic disrupted health care delivery of cancer screenings. The primary aim of our work was to evaluate the degree to which populations were accepting of home-based screenings for colorectal cancer (CRC) and cervical cancer (ie, primary human papillomavirus [HPV] testing). Three groups of adults having distinct health burdens that may affect acceptance of home-based cancer screening were identified through outpatient electronic medical records: those having survived a COVID-19 hospitalization; those having been positive for a non-COVID-19 respiratory illness; or those having type 2 diabetes. A total of 132 respondents (58% female) completed an online survey with hypothetical cases about their acceptance of home-based CRC or cervical cancer screening. Among women respondents, urine and vaginal screening for primary HPV testing was acceptable to 64% and 59%, respectively. Among both men and women, at-home CRC screening with fecal immunochemical test or Cologuard ® was acceptable to 60% of the respondents. When adjusting for education, women with a positive attitude toward home-based urine and vaginal screening were 49 times and 23 times more likely, respectively, to have a positive attitude toward CRC screening. These findings indicate that home-based cancer screens for CRC and primary HPV testing are acceptable to men and women and may allow for greater compliance with screening in the future., Competing Interests: Conflicts of Interest None., (© 2021 Aurora Health Care, Inc.)

Competing Interests: We declare no competing interests.

Objective: To determine characteristics of providers marketing vasectomy reversal (VR) online, degree of information available online, the ease with which patients can compare providers, and the differences in VR practice patterns between academic and private practices., Materials and Methods: We identified VR practices operating within the top 50 most populous metropolitan areas in the US. Practice websites were reviewed to obtain information such as provider educational background, level of magnification, ability to perform vasoepididymostomy, surgical volume, and cost. Based on information available, providers were assigned a novel REVERSAL score created by the authors. Descriptive statistics were used to compare results., Results: Of the 107 providers identified (29 academic, 78 private), the majority were male urologists with a Doctor of Medicine degree. Academic providers were more likely to have fellowship training than private practice providers, 96.6 vs 43.6%, respectively (P = 0.00001). Compared to non-urologists, urologists were less likely to purchase online ads or disclose cost. Non-urologists charged significantly less than urologists, $3,584 ± 1,554 and $6,591 ± 1,518, respectively (P = 0.00001). Only one provider provided complete information as defined by REVERSAL score of 12, with the majority (61.7%) of providers achieving score ≤6., Conclusion: There is significant lack of transparency in publicly available information from VR practices. Practices should implement measures to improve dissemination of information to the public, so that patients can more easily compare providers and make informed decisions regarding VR., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ultrasound imaging presents many positive attributes, including safety, real-time imaging, universal accessibility, and cost. However, inherent difficulties in discrimination between soft tissues and tumors prompted development of stabilized microbubble contrast agents. This presents the opportunity to develop agents in which drug is entrapped in the microbubble shell. We describe preparation and characterization of theranostic poly(lactide) (PLA) and pegylated PLA (PEG-PLA) shelled microbubbles that entrap gemcitabine, a commonly used drug for pancreatic cancer (PDAC). Entrapping 6 wt% gemcitabine did not significantly affect drug activity, microbubble morphology, or ultrasound contrast activity compared with unmodified microbubbles. In vitro microbubble concentrations yielding ≥ 500nM entrapped gemcitabine were needed for complete cell death in MIA PaCa-2 PDAC drug sensitivity assays, compared with 62.5 nM free gemcitabine. In vivo administration of gemcitabine-loaded microbubbles to xenograft MIA PaCa-2 PDAC tumors in athymic mice was well tolerated and provided substantial tumoral image enhancement before and after destructive ultrasound pulses. However, no significant differences in tumor growth were observed among treatment groups, in keeping with the in vitro observation that much higher doses of gemcitabine are required to mirror free gemcitabine activity. STATEMENT OF SIGNIFICANCE: The preliminary results shown here are encouraging and support further investigation into increased gemcitabine loading. Encapsulation of gemcitabine within polylactic acid (PLA) microbubbles does not damage its activity towards pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) cells. Excellent imaging and evidence of penetration into the highly desmoplastic PDAC tumors is demonstrated. Microbubble destruction was confirmed in vivo, showing that elevated mechanical index shatters the microbubbles for enhanced delivery. The potential to slow PDAC growth in vivo is shown, but higher gemcitabine concentrations are required. Current efforts are directed at increasing drug loading by inclusion of drug-carrying nanoparticles for effective in vivo treatment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Flemming Forsberg acknowledges equipment support from Siemens Healthineers. John Eisenbrey acknowledges equipment support from Siemens, grant funding and equipment support from GE Healthcare, and drug support and speaker fees from Lantheus Medical Imaging. Lauren Delaney, David Brown, Jonathan Brody, Masaya Jimbo, Brian Oeffinger, Maria Stanczak, Ji-Bin Liu, and Margaret Wheatley have no competing interests to report., (Copyright © 2021. Published by Elsevier Ltd.)

Background/aims: Postoperative adhesions may induce adverse outcomes in patients. Adhesion formation is initiated by fibrin accumulation at the surgical site which is followed by local neutrophilia and the establishment of neutrophil extracellular traps (NET). Previous reports have suggested that the preventive efficacy of reagents designed to reduce postoperative adhesion is inversely correlated with neutrophilia and NET production. Antithrombin (AT) is a natural inhibitor of thrombin, a key factor in coagulation. Here, we evaluate whether treatment with AT and/or NET inhibitors prevent or reduce postoperative adhesion formation in mice., Methods: Mice were treated with AT and/or NET inhibitors before and/or after cecum cauterization and their adhesion scores were evaluated on day 7 post-operation. Immunochemistry/ immunofluorescence analyses were also performed and we used GSK484, an inhibitor of peptidyl arginine deiminase 4 (PAD4), as the NET inhibitor., Results: AT or GSK484 partially rescued postoperative adhesion formation in mice. AT prevented thrombin-induced plasminogen activator inhibitor 1 and interleukin-6 expression in mesothelial cells in vitro. However, AT could not prevent neutrophilia or NETs formation around the injured serosa. Finally, we investigated a combination of AT and a PAD4 inhibitor and found that this could inhibit almost all adhesion formation in these animals. Since AT-inactivating proteases are liberated following NET release, they might dampen the biological action of the AT treatment. This suggests that NET inhibitors might allow AT to exert its full action in the surgically injured serosa., Conclusion: Combined treatment with AT and GSK484 may effectively attenuate postoperative adhesion production in mice., Competing Interests: All of the authors have no conflicts of interest., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Objective: To evaluate clinical characteristics associated with patient attitudes toward surgical treatment of Peyronie's disease (PD) prior to consultation in a high-volume male sexual health clinic., Methods: From 2014-2018 a prospective database was created of patients presenting to the sexual health clinic at our institution. Multivariable regression analysis was conducted to determine factors associated with pre-visit consideration of surgery., Results: Of 1359 men presenting to clinic, 342 had a chief complaint of PD. Prior to consultation, 79% of patients (n = 270) stated they were willing to consider surgery to correct their PD symptoms. Factors associated with consideration of surgery included younger patient age (mean 55.8 vs 60.0 years; P = .008), history of depression/anxiety (21% vs 8%, P = .01), greater penile curvature (43.3 vs 34.6 degrees; P = .002), penile shortening (64% vs 44%; P = .003), pain with erections (46% vs 33%; P = .05) and decreased ability to have penetrative intercourse (51.9% vs 65.3%, P = .04). On multivariable analysis, age, history of depression, penile shortening, and mean curvature remained significantly associated. Symptom duration and relationship factors were not associated with a difference in the stated preference to consider surgery prior to consultation (P >.05 for all)., Conclusion: Nearly 4 out of 5 patients reported willingness to consider surgical intervention for their PD-related symptoms prior to urologic consultation. On multivariable analysis, younger age, history of depression/anxiety, penile shortening, and curvature were associated with a greater likelihood of considering surgery. This information provides important insight into patient attitude toward undergoing surgery and will help drive patient counseling for men with PD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Most corals acquire symbiodiniacean symbionts from the surrounding environment to initiate symbiosis. The cell densities of Symbiodiniaceae in the environment are usually low, and mechanisms may exist by which new coral generations attract suitable endosymbionts. Phototaxis of suitable symbiodiniacean cells toward green fluorescence in corals has been proposed as one such mechanism. In the present study, we observed the phototaxis action wavelength of various strains of Symbiodiniaceae and the fluorescence spectra of aposymbiotic Acropora tenuis larvae at the time of endosymbiont uptake. The phototaxis patterns varied among the Symbiodiniaceae species and "native" endosymbionts-commonly found in Acropora juveniles present in natural environments; that is, Symbiodinium microadriaticum was attracted to blue light rather than to green light. Another native endosymbiont, Durusdinium trenchii, showed no phototaxis specific to any wavelength. Although the larvae exhibited green and broad orange fluorescence under blue-violet excitation light, the maximum green fluorescence peak did not coincide with that of the phototaxis action spectrum of S. microadriaticum. Rather, around the peak wavelength of larval green fluorescence, this native endosymbiont showed slightly negative phototaxis, suggesting that the green fluorescence of A. tenuis larvae may not play a role in the initial attraction of native endosymbionts. Conversely, broad blue larval fluorescence under UV-A excitation covered the maximum phototaxis action wavelength of S. microadriaticum. We also conducted infection tests using native endosymbionts and aposymbiotic larvae under red LED light that does not excite visible larval fluorescence. Almost all larvae failed to acquire S. microadriaticum cells, whereas D. trenchii cells were acquired by larvae even under red illumination. Thus, attraction mechanisms other than visible fluorescence might exist, at least in the case of D. trenchii. Our results suggest that further investigation and discussion, not limited to green fluorescence, would be required to elucidate the initial attraction mechanisms., Competing Interests: The authors have declared that no competing interests exist.

Middle Eastern/North Africa (MENA) women are often not identified in cancer screening studies. The aim of this study was to determine the rates and predictors of cervical and colorectal cancer (CRC) screening for women 50-65 years of three race/ethnicities. White, black and MENA women of Southeast Michigan were surveyed once in 2019 for demographics, health care barriers, chronic diseases, and cancer screening updates using in-person, telephone, and online methods. Descriptive statistics and multivariate multinomial logistic regression were used to predict up-to-date colorectal cancer and cervical cancer screening. All analyses were adjusted by local population weights for comparability and generalizability. 394 women participated with 54% up-to-date on both screenings, 21% for cervical cancer screening alone, and 12% for CRC alone. Women more likely to be up-to-date for only cervical cancer screening compared to both cancer screens are younger (aOR 0.83 (95% CI 0.76, 0.92), are of MENA descent (7.97 (2.46, 25.76) and have no insurance (9.41 (1.07, 82.92). There are no predictors for women being up-to-date for CRC screening alone compared to both screens. Among women 50-65 years old, being up-to-date in cervical cancer screening is unrelated to being up-to-date for CRC screening. Compared to Healthy People 2020, there are significant gaps in cervical and CRC screening among women 50-65 years old of all races, but particularly among women of MENA descent who are even less likely to have CRC screening than cervical cancer screening., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Inc.)

The objective of this study is to identify factors associated with bother with rapid ejaculation in a cohort of men presenting to a sexual dysfunction clinic, independent of a diagnosis of PE. A prospective institutional database has been maintained on patients completing an 89-item intake questionnaire querying various areas of sexual dysfunction. Regarding ejaculatory dysfunction, patients are asked "Do you feel bothered, annoyed, and/or frustrated by ejaculating too quickly?" Statistical modeling was performed to identify associations. A total of 1359 men completed the intake survey, and 694 responded to the question on bother with rapid ejaculation. Overall, 42.9% (298/694) of respondents reported bother with rapid ejaculation. Men reporting bother were more likely to report lower intravaginal ejaculatory latency (IELT) time (4.2 vs 12.2 min, p < 0.0001), problems with depression (32% vs 21%, p = 0.001), negative impact on relationship (73% vs 51%, p < 0.0001), and negative impact on partner's sexual satisfaction (26% vs 15%, p < 0.001). These results highlight the importance of asking all men presenting with sexual health concerns about their bother with rapid ejaculation for complete assessment of sexual and mental wellbeing.

Body condition in mammals fluctuates depending on energy intake and expenditure. For brown bears ( Ursus arctos ), high-protein foods facilitate efficient mass gain, while lipids and carbohydrates play important roles in adjusting dietary protein content to optimal levels to maximize energy intake. On the Shiretoko Peninsula, Hokkaido, Japan, brown bears have seasonal access to high-lipid pine nuts and high-protein salmon. To assess seasonal and annual fluctuation in the body condition of adult female brown bears in relation to diet and reproductive status, we conducted a longitudinal study in a special wildlife protection area on the Shiretoko Peninsula during 2012-2018. First, analyses of 2,079 bear scats revealed that pine nuts accounted for 39.8% of energy intake in August and salmon accounted for 46.1% in September and that their consumption by bears varied annually. Second, we calculated the ratio of torso height to torso length as an index of body condition from 1,226 photographs of 12 adult females. Results indicated that body condition continued to decline until late August and started to increase in September when salmon consumption increased. In addition, body condition began to recover earlier in years when consumption of both pine nuts and salmon was high. Furthermore, females with offspring had poorer body condition than solitary females, in particular in late August in years with low salmon consumption. Our findings suggest that coastal and subalpine foods, which are unique to the Shiretoko Peninsula, determine the summer body condition of female brown bears, as well as their survival and reproductive success., Competing Interests: The authors have no conflict of interest to declare., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

To test the hypothesis that terrestrial runoff affects the functions of calcareous sediments in coral reefs and hampers the development of corals, we analysed calcareous sediments with different levels of bound phosphate, collected from reef areas of Okinawajima, Japan. We confirmed that phosphate bound to calcareous sediments was readily released into ambient seawater, resulting in much higher concentrations of phosphorous in seawater from heavily polluted areas (4.3-19.0 µM as compared with less than 0.096 µM in natural ambient seawater). Additionally, we examined the effect of phosphate released from calcareous sediments on the development of Acropora digitifera coral juveniles. We found that high phosphate concentrations in seawater clearly inhibit the skeletal formation of coral juveniles. Our results demonstrate that calcareous sediments in reef areas play a crucial role in mediating the impact of terrestrial runoff on corals by storing and releasing phosphate in seawater., (© 2021 The Authors.)

Many corals establish symbiosis with Symbiodiniaceae cells from surrounding environments, but very few Symbiodiniaceae cells exist in the water column. Given that the N -acetyl-d-glucosamine-binding lectin ActL attracts Symbiodiniaceae cells, we hypothesized that corals must attract Symbiodiniaceae cells using ActL to acquire them. Anti-ActL antibody inhibited acquisition of Symbiodiniaceae cells, and rearing seawater for juvenile Acropora tenuis contained ActL, suggesting that juvenile A. tenuis discharge ActL to attract these cells. Among eight Symbiodiniaceae cultured strains, ActL attracted NBRC102920 ( Symbiodinium tridacnidorum ) most strongly followed by CS-161 ( Symbiodinium tridacnidorum ), CCMP2556 ( Durusdinium trenchii ), and CCMP1633 ( Breviolum sp.); however, it did not attract GTP-A6-Sy ( Symbiodinium natans ), CCMP421 ( Effrenium voratum ), FKM0207 ( Fugacium sp.), and CS-156 ( Fugacium sp.). Juvenile polyps of A. tenuis acquired limited Symbiodiniaceae cell strains, and the number of acquired Symbiodiniaceae cells in a polyp also differed from each other. The number of Symbiodiniaceae cells acquired by juvenile polyps of A. tenuis was correlated with the ActL chemotactic activity. Thus, ActL could be used to attract select Symbiodiniaceae cells and help Symbiodiniaceae cell acquisition in juvenile polyps of A. tenuis , facilitating establishment of symbiosis between A. tenuis and Symbiodiniaceae cells.

Lay Summary: During the coronavirus disease 2019 (COVID-19) pandemic, cancer screening decreased precipitously; home screening for colorectal cancer diminished less than that for colonoscopy and breast and cervical cancer screening. The authors have highlighted approaches for home cancer screening in addition to telemedicine., (© 2020 American Cancer Society.)

Background/aims: Although adhesion formation is a frequent adverse event following intraperitoneal surgery, efficient prophylactic interventions have not yet been established. We recently reported that blockade of interleukin (IL)-6 prevented postoperative adhesion after cecum cauterization. Intriguingly, this intervention dampened tumor necrosis factor (TNF) induction in the injured serosa. Herein, we addressed whether TNF might be a key target and, if so, how TNF blockade rescued adhesion formation., Methods: Mice were administered an anti-TNF biologic (etanercept) on days -2 and -1 before and upon cecal cauterization. The adhesion scores were evaluated at day 7 postoperatively. Histological alterations were examined by immunochemistry/immunofluorescence studies. We incubated human neutrophils and mesothelial cell line cells with recombinant TNF in the presence of etanercept and measured transcript levels of cytokines and chemokines by quantitative reverse transcription-polymerase chain reaction (RT-qPCR)., Results: Etanercept rescued mice from adhesion formation, accompanied by a robust reduction of neutrophilia in the injured serosa. Immunofluorescence revealed a substantial formation of neutrophil extracellular traps (NETs) with the potential to induce tissue damage and profibrotic responses. In contrast, the etanercept-treated mice lacked NET formation. In addition, etanercept inhibited TNF-induced IL-6, TNF, and neutrophil-recruiting chemokines in neutrophils and mesothelial cells, a major cellular source of myofibroblasts in the adhesion band., Conclusion: Prophylactic administration of etanercept might be a potential strategy for preventing postoperative adhesion formation., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

Human habituation of large carnivores is becoming a serious problem that generates human-wildlife conflict, which often results in the removal of animals as nuisances. Although never tested, human habituation potentially reduces the fitness of adult females by reducing their offspring's survival as well as their own, due to an increased likelihood of human-caused mortality. Here, we tested this hypothesis in brown bears inhabiting Shiretoko National Park, Japan. We estimated the frequency of human-caused mortality of independent young (aged 1-4 years) born to mothers living in areas with different maternal levels of human habituation and different proximities to areas of human activity. The overall mortality rate was higher in males than in females, and in females living near a town than those in a remote area of park. Surprisingly, more than 70% of males born to highly habituated mothers living around a remote wildlife protection area were killed by humans; this proportion is greater than that for males born to less-habituated mothers living in almost the same area. The current study clarified that interactions among maternal human habituation, birthplace (proximity to town), age, and sex determine the likelihood of human-caused mortality of brown bears at an early stage of life.

Body condition is an important determinant of health, and its evaluation has practical applications for the conservation and management of mammals. We developed a noninvasive method that uses photographs to assess the body condition of free-ranging brown bears ( Ursus arctos ) in the Shiretoko Peninsula, Hokkaido, Japan. First, we weighed and measured 476 bears captured during 1998-2017 and calculated their body condition index (BCI) based on residuals from the regression of body mass against body length. BCI showed seasonal changes and was lower in spring and summer than in autumn. The torso height:body length ratio was strongly correlated with BCI, which suggests that it can be used as an indicator of body condition. Second, we examined the precision of photograph-based measurements using an identifiable bear in the Rusha area, a special wildlife protection area on the peninsula. A total of 220 lateral photographs of this bear were taken September 24-26, 2017, and classified according to bear posture. The torso height:body/torso length ratio was calculated with four measurement methods and compared among bear postures in the photographs. The results showed torso height:horizontal torso length (TH:HTL) to be the indicator that could be applied to photographs of the most diverse postures, and its coefficient of variation for measurements was <5%. In addition, when analyzing photographs of this bear taken from June to October during 2016-2018, TH:HTL was significantly higher in autumn than in spring/summer, which indicates that this ratio reflects seasonal changes in body condition in wild bears. Third, we calculated BCI from actual measurements of seven females captured in the Rusha area and TH:HTL from photographs of the same individuals. We found a significant positive relationship between TH:HTL and BCI, which suggests that the body condition of brown bears can be estimated with high accuracy based on photographs. Our simple and accurate method is useful for monitoring bear body condition repeatedly over the years and contributes to further investigation of the relationships among body condition, food habits, and reproductive success., Competing Interests: The authors declare there are no competing interests. Masami Yamanaka, Masanao Nakanishi, and Tsuyoshi Ishinazaka are employed by the Shiretoko Nature Foundation., (©2020 Shirane et al.)

A uterine rupture may result in a massive hemoperitoneum, which can be fatal to both the fetus and mother. Most uterine ruptures during pregnancy occur within a scarred uterus, rarely occurring in an unscarred uterus. Here, we report a very rare case of spontaneous rupture in an unscarred uterus at 11 weeks of gestation of a twin pregnancy and its surgical repair. A 37-year-old nulliparous infertile woman became pregnant with twins after artificial insemination and gonadotropin therapy. She underwent emergency surgery at 11 weeks of gestation due to an acute abdomen caused by massive hemoperitoneum. Upon laparotomy, one fetus with placenta was extruded into the abdominal cavity through a 3-cm myometrium rupture on the left posterior wall of the uterus. After surgical repair of the rupture site, the remaining fetus was alive and was successfully delivered by cesarean section at 34 weeks of gestation., (© 2020 Japan Society of Obstetrics and Gynecology.)

Nitrous oxide (N 2 O) is underutilized in ambulatory urology. Here, we review available data regarding application, efficacy, and side effect profile of N 2 O in ambulatory urologic procedures. Data were available from 11 studies. N 2 O has been described in the setting of transrectal ultrasound-guided prostate biopsies, flexible cystoscopy, ureteral stent placement, and extracorporeal shockwave lithotripsy in adult patients and catheterization in children. Studies showed significant improvements in peri-procedural pain and anxiety relative to alternative (or none) forms of analgesia. Adverse effects were rare and self-limited. More widespread use of N 2 O may result in cost savings and better patient tolerance with outpatient procedures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Colorectal cancer screening has been shown to prevent or detect early colorectal cancer and reduce mortality; yet, adherence to screening recommendations remains low, particularly in rural settings., Study Design: RCT., Setting/participants: Adults (n=7,812) aged 50-75 years and due for colorectal cancer screening in a largely rural health system were randomly assigned to either the intervention (n=3,906) or the control (n=3,906) group in September 2016, with analysis following through 2018., Intervention: A mailed motivational messaging screening reminder letter with an option to call and request a free at-home fecal immunochemical screening test (intervention) or the standard invitation letter detailing that the individual was due for screening (control). Multifaceted motivational messaging emphasized colorectal cancer preventability and the ease and affordability of screening, and communicated a limited supply of test kits., Main Outcome Measures: Colorectal cancer screening participation within 6 months after mailed invitation was ascertained from the electronic medical record., Results: Colorectal cancer screening participation was significantly improved in the intervention (30.1%) vs the usual care control group (22.5%; p<0.001). Individuals randomized to the intervention group had 49% higher odds of being screened over follow-up than those randomized to the control group (OR=1.49, 95% CI=1.34, 1.65). A total of 13.2 screening invitations were needed to accomplish 1 additional screening over the usual care. Of the 233 fecal immunochemical test kits mailed to participants, 154 (66.1%) were returned, and 18 (11.7%) tested positive., Conclusions: A mailed motivational messaging letter with a low-cost screening alternative increased colorectal cancer screening in this largely rural community with generally poor adherence to screening recommendations. Mailed colorectal cancer screening reminders using motivational messaging may be an effective method for increasing screening and reducing rural colorectal cancer disparities., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Climacturia is an under-reported complication of definitive therapy for prostate cancer (PCa) - that is, radical prostatectomy (RP) and/or radiation therapy (RT)., Aim: We sought to identify the prevalence and predictors of climacturia and associated patient/partner bother in patients with and without prior PCa treatment., Methods: We analyzed a database of patients who presented to our Men's Health clinic and filled out a questionnaire related to sexual function and pertinent medical histories. The prevalence of climacturia and associated patient/partner bother in patients with/without prior RP/RT was calculated. Univariable and multivariable logistic regressions were performed to identify predictors associated with climacturia and patient/partner bother., Outcomes: The primary outcomes were the prevalence and predictors of climacturia and associated patient/partner bother in patients with/without history of definitive PCa treatment., Results: Among 1,117 patients able to achieve orgasm, 192 patients (17%) had prior history of definitive therapy for PCa (RP alone = 139 [72%]; RT alone = 22 [11%]; RP + RT = 31 [16%]). Climacturia was reported by 39%, 14%, 52%, and 2.4% of patients with history of RP alone, RT alone, RP + RT, and neither RP nor RT, respectively (P < .05 between all groups). 33 to 45 percent of patients with climacturia noted significant patient/partner bother. Factors significantly associated with climacturia were prior RP, prior RT, history of other prostate surgery, and erectile dysfunction, although erectile dysfunction was not significant on multivariable analysis. Significant reduction in climacturia prevalence was noted for patients who were ≥1 year out from RP, compared with patients who were <1 year out. Among patients with prior RP/RT, stress urinary incontinence was associated with increased risk of climacturia, whereas diabetes was associated with decreased risk. No factors were associated with patient/partner bother. Among patients with prior RP, nerve-sparing technique did not predict presence of climacturia but was associated with reduced patient/partner bother., Clinical Translation: Given significant prevalence of climacturia and associated patient/partner bother, patients should be counseled on the risk of climacturia before undergoing RP/RT., Strengths and Limitations: Strengths include the large study population and the focus on both RP and RT. Limitations include the facts that this is a single-institution study that primarily relies on patients' subjective reporting and that the study population may not represent the general population., Conclusions: Climacturia affects a significant proportion of patients with history of RP/RT for PCa, and many patients and their partners find this bothersome. Jimbo M, Alom M, Pfeifer ZD, et al. Prevalence and Predictors of Climacturia and Associated Patient/Partner Bother in Patients With History of Definitive Therapy for Prostate Cancer. J Sex Med 2020;17:1126-1132., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: There are limited published data characterizing pediatric burn patients with genital burns (GB)., Objective: Assess prevalence of GB in pediatric burn patients and analyze clinical characteristics including predictors of mortality., Study Design: We queried American Burn Association's National Burn Repository to identify all pediatric burn patients who presented to North American burn centers over a 10-year period. We excluded all patients aged ≥18 years and patients with unknown sex, race, and/or mortality. We also excluded subsequent encounters for patients with multiple visits. Demographic and clinical characteristics were compared between patients with and without GB. Univariable and multivariable logistic regression analyses were performed to identify predictors of mortality., Results: Among 38 211 pediatric burn patients, 1244 (3.3%) suffered from second- or third-degree GB. Patients who suffered from third-degree GB (GB3) were significantly older than patients who suffered from second-degree GB (GB2) or patients without GB. Of the patients, 32.3% were aged 0-2 years. Scalding was the most common mechanism of injury for pediatric GB patients at 73.8%. Compared to non-GB patients, GB patients had significantly higher total body surface area (TBSA) burned (16.5% vs 7.0%), higher rates of associated inhalation injury (4.1% vs 2.6%), longer length of stay (LOS) (14.3 days vs 6.7 days), higher rates of urinary tract infection (UTI) (13.0% vs 2.8%) and sepsis (14.1% vs 2.3%), and higher mortality (3.5% vs 0.7%) (P < 0.0001 for all). The differences were more pronounced for the subset of patients who suffered from GB3 (TBSA 43.5%, associated inhalation injury 19.9%, LOS 42.9 days, 21.3% UTI, 33.3% sepsis, and 19.3% mortality). On multivariable analysis, the presence of GB3, TBSA, non-white ethnicity, and the presence of associated inhalation injury were significant predictors of mortality. Only 4.5% of pediatric GB patients underwent genital surgery, with the majority consisting of excision, reconstruction, or repair of the penis, vulva, or perineum. No patient required orchiectomy or suprapubic catheter placement., Discussion: This is the largest study to date of pediatric GB patients. A minority of pediatric burn patients present with GB. However, when they occur, GB are associated with significantly worse clinical outcomes. Importantly, the presence of GB3 is an independent predictor of mortality in pediatric burn patients., Conclusion: The presence of GB appears to be a strong marker of severe burn injury. Pediatric GB patients need to be carefully assessed and aggressively managed for additional injuries, complications, surgical needs, and mortality risk., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

Symbiosis with zooxanthellae is essential for survival of corals. Using a bioassay, we report the H-type lectin SLL-2 purified from the octocoral Sinularia lochmodes to restrict zooxanthellae form to spherical cells. However, the factor for initiating or maintaining a symbiotic relationship between a host and zooxanthellae has not been found in many corals. This bioassay is useful for evaluating the role of a lectin as a symbiosis-related factor.

Background: Large scale United States (US) surveys guide efforts to maximize the health of its population. Cervical cancer screening is an effective preventive measure with a consistent question format among surveys. The aim of this study is to describe the predictors of cervical cancer screening in older women as reported by three national surveys., Methods: The Behavioral Risk Factor Surveillance System (BRFSS 2016), the Health Information National Trends Survey (HINTS 2017), and the Health Center Patient Survey (HCPS 2014) were analyzed with univariate and multivariate analyses. We defined the cohort as women, without hysterectomy, who were 45-65years old. The primary outcome was cytology within the last 3years., Results: Overall, Pap screening rates were 71% (BRFSS), 79% (HINTS) and 66% (HCPS), among 41,657, 740 and 1571 women, respectively. BRFSS showed that women 60-64years old (aPR=0.88, 95% CI: 0.85, 0.91), and in rural locations (aPR=0.95, 95% CI: 0.92, 0.98) were significantly less likely to report cervical cancer screening than women 45-49-years old or in urban locations. Compared to less than high school, women with more education reported more screening (aPR=1.20, 95% CI: 1.13, 1.28), and those with insurance had higher screening rates than the uninsured (aPR=1.47, 95% CI: 1.33, 1.62). HINTS and HCPS also showed these trends., Conclusions: All three surveys show that cervical cancer screening rates in women 45-65years are insufficient to reduce cervical cancer incidence. Insurance is the major positive predictor of screening, followed by younger age and more education. Race/ethnicity are variable predictors depending on the survey., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Postpartum hemorrhage within 24 hours after delivery remains the leading cause of maternal mortality worldwide. Puerperal genital hematoma (PGHA) is a rare complication of postpartum hemorrhage, and PGHA can be life-threatening if hemostasis is not properly achieved. However, a reliable management algorithm for PGHA based on the clinical findings has not been developed. The objectives were to evaluate the management strategies for PGHA and identify the clinical findings that help select the treatment for PGHA. The medical records of women who were treated for PGHA in our department were reviewed, and data regarding the clinical findings and the treatment strategy for PGHA were analyzed. Thirty-four women who underwent treatment for PGHA were identified and divided into three groups according to the final procedure that achieved hemostasis: conservative management (CM) (n = 9), surgical management (SURG) (n = 15), and arterial embolization management (AEM) (n = 10). Regarding the clinical findings on initial evaluation, the shock index was significantly higher in the AEM group than in the CM or SURG group; and initial platelet count and fibrinogen level were significantly lower in the AEM group than in the CM group. There was no significant difference in any computed tomography (CT) finding among the three groups. In conclusion, this study clearly shows the difference in clinical findings among treatment strategies for PGHA. We suggest that the clinical findings of shock index, platelet count, and fibrinogen level together with CT findings are helpful and valuable for selecting the treatment strategy for PGHA.

Biomedical data often includes personal information, and the technology is demanded that enables the searching of such sensitive data while protecting privacy. We consider a case in which a server has a text database and a user searches the database to find substring matches. The user wants to conceal his/her query and the server wants to conceal the database except for the search results. The previous approach for this problem is based on a linear-time algorithm in terms of alphabet size $\mathbf{|\Sigma |}$|Σ|, and it cannot search on the database of large alphabet such as biomedical documents. We present a novel algorithm that can search a string in logarithmic time of $\mathbf{|\Sigma |}$|Σ|. In our algorithm, named secure wavelet matrix (sWM), we use an additively homomorphic encryption to build an efficient data structure called a wavelet matrix. In an experiment using a simulated string of length 10,000 whose alphabet size ranges from 4 to 1024, the run time of the sWM was up to around two orders of magnitude faster than that of the previous method. sWM enables the searching of a private database efficiently and thus it will facilitate utilizing sensitive biomedical information.

Introduction: Colorectal cancer screening (CRCS) remains underutilized. Decision aids (DAs) can increase patient knowledge, intent, and CRCS rates compared with "usual care," but whether interactivity further increases CRCS rate remains unknown., Study Design: A two-armed RCT compared the effect of a web-based DA that interactively assessed patient CRC risk and clarified patient preference for specific CRCS test to a web-based DA with the same content but without the interactive tools., Setting/participants: The study sites were 12 community- and three university-based primary care practices (56 physicians) in southeastern Michigan. Participants were men and women aged 50-75 years not current on CRCS., Intervention: Random allocation to interactive DA (interactive arm) or non-interactive DA (non-interactive arm)., Main Outcome Measures: Primary outcome was medical record documentation of CRCS 6 months after the intervention. Secondary outcome was patient decision quality (i.e., knowledge, preference clarification, and intent) measured immediately before and after DA use, and immediately after the office visit. To determine that either DA had a positive effect on CRCS adherence, usual care CRCS rates were determined from the three university-based practices among patients eligible for but not participating in the study., Results: Data were collected between 2012 and 2014; analysis began in 2015. At 6 months, CRCS rate was 36.1% (95% CI=30.5%, 42.2%) in the interactive arm (n=284) and 40.5% (95% CI=34.7%, 46.6%) in the non-interactive arm (n=286, p=0.29). Usual care CRCS rate (n=440) was 18.6% (95% CI=15.2%, 22.7%), significantly lower than both arms (p<0.001). Knowledge, attitude, self-efficacy, test preference, and intent increased significantly within each arm versus baseline, but the rate was not significantly different between the two arms., Conclusions: The interactive DA did not improve the outcome compared to the non-interactive DA. This suggests that the resources needed to create and maintain the interactive components are not justifiable., Trial Registration: This study is registered at www.clinicaltrials.gov NCT01514786., (Copyright © 2019. Published by Elsevier Inc.)

A novel protein, soritesidine (SOR) with potent toxicity was isolated from the marine sponge Spongosorites sp. SOR exhibited wide range of toxicities over various organisms and cells including brine shrimp ( Artemia salina ) larvae, sea hare ( Aplysia kurodai ) eggs, mice, and cultured mammalian cells. Toxicities of SOR were extraordinary potent. It killed mice at 5 ng/mouse after intracerebroventricular (i.c.v.) injection, and brine shrimp and at 0.34 µg/mL. Cytotoxicity for cultured mammalian cancer cell lines against HeLa and L1210 cells were determined to be 0.062 and 12.11 ng/mL, respectively. The SOR-containing fraction cleaved plasmid DNA in a metal ion dependent manner showing genotoxicity of SOR. Purified SOR exhibited molecular weight of 108.7 kDa in MALDI-TOF MS data and isoelectric point of approximately 4.5. N -terminal amino acid sequence up to the 25th residue was determined by Edman degradation. Internal amino acid sequences for fifteen peptides isolated from the enzyme digest of SOR were also determined. None of those amino acid sequences showed similarity to existing proteins, suggesting that SOR is a new proteinous toxin.

Coral reef degradation due to various local stresses, such as nutrient enrichment and terrestrial run-off into coastal waters, is an increasing global concern. Inorganic phosphates have been considered to possibly inhibit skeleton formation in corals. Despite many studies available on the effects of nutrients on corals, a clear consensus on how nutrients exert deteriorative effects on corals has not been established satisfactorily. In this study, we examined the effects of phosphates and nitrates on in vitro aragonite CaCO 3 formation by using biogenic polyamines and in vivo aragonite formation in the skeleton of juvenile Acropora digitifera corals. We showed that the phosphates at similar concentrations clearly inhibited both in vitro and in vivo CaCO 3 formation. In contrast, nitrates inhibited neither in vitro aragonite CaCO 3 formation nor in vivo aragonite formation in juvenile coral skeleton. Furthermore, our findings showed that inhibition of coral skeleton formation was due to absorption of phosphate on the skeleton, which inorganically inhibited normal development of juvenile coral skeleton.

Purpose: Transparency of conflicts of interest is essential when assessing publications that address the benefits of robotic surgery over traditional laparoscopic and open operations. We assessed discrepancies between self-reported and actual conflicts of interest as well as whether conflicts of interest are associated with favorable endorsement of robotic surgery., Materials and Methods: We searched the Embase® and MEDLINE® databases for articles on robotic surgery within pediatric urology. We included English language articles published since 2013, when data in the Open Payments program (Centers for Medicare and Medicaid Services, Baltimore, Maryland) became available. For all United States based authors Open Payments was used to identify the total amount of financial payment received from Intuitive Surgical®. Chi-square test was used to assess the association between conflicts of interest and favorable endorsement of robotic surgery., Results: A total of 191 articles were initially identified. After exclusion criteria were applied 107 articles remained (267 distinct authors). Of the articles 86 (80.4%) had at least 1 author with a history of payment from Intuitive Surgical, with 79 (91.9%) having at least 1 author who did not declare a conflict of interest despite history of payment. A total of 44 authors (16.5%) had a history of payment from Intuitive Surgical, with an average payment of $3,594.15. Articles with a first and/or last author with a history of payment were more likely to contain a favorable endorsement of robotic surgery compared to articles without a history of payment (85.1% vs 63.6%, p = 0.0124)., Conclusions: Nondisclosure of conflict of interest with Intuitive Surgical is extremely common within pediatric urology. Steps to ensure accurate reporting of conflicts of interest are essential. There appears to be an association between a history of payment and favorable endorsement of robotic surgery.

Transvaginal cervicoisthmic cerclage was carried out in 12 such patients who were at high-risk of premature delivery. Patients who underwent transvaginal cervicoisthmic cerclage had undergone conization, cervical radical hysterectomy or another form of extensive cervical resection, or had a history of third-trimester miscarriage or premature delivery despite having previously undergone cervical cerclage several times for cervical incompetence. There were seven cases of pregnancy after extensive conization, and four had a history of failed cervical cerclage. Two of these cases were the same individual, who became pregnant twice after extensive conization and gave birth to a live infant each time. The mean age at surgery was 35.7 years, and cerclage was performed at 11-19 weeks' gestation. All of the infants survived to hospital discharge. Transvaginal cervicoisthmic cerclage may be considered effective for patients with the history of recurring pregnancy loss due to previous failure of prophylactic cerclage., (© 2018 Japan Society of Obstetrics and Gynecology.)

Biogenic polyamines are involved in a wide range of plant cellular processes, including cell division, morphogenesis and stress responses. However, the exact roles of biogenic polyamines are not well understood. We recently reported that biogenic polyamines that have multiple amino groups can react with CO 2 and accelerate calcium carbonate formation in seawater. The ability of biogenic polyamines to capture atmospheric CO 2 prompted us to examine their roles in photosynthesis. Here, we demonstrated that atmospheric CO 2 captured by biogenic polyamines is a candidate substrate for the carboxylation reaction of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), which is an enzyme involved in the first major step of carbon fixation during photosynthesis, and that biogenic polyamines can accelerate the carboxylation reaction of this enzyme because of their specific affinity for CO 2 . Moreover, the results of our nuclear magnetic resonance (NMR) analysis showed that putrescine, which is the most common biogenic polyamine, reacts with atmospheric CO 2 and promotes the formation of carbamate derivatives and bicarbonate in aqueous environments. A sufficient amount of CO 2 is well known to be produced by carbonic anhydrase from bicarbonate in vivo. The present study indicates that CO 2 would be also produced by the equilibrium reaction from carbonate produced by biogenic polyamines and would be used as a substrate of Rubisco, too. Our results may suggest a new photosynthetic research strategy that involves CO 2 -concentrating mechanisms and also possibly constitutes a potential tool for reducing atmospheric CO 2 levels and, consequently, global warming.

Testicular torsion remains the most frequent cause of testicular ischemia, especially in adolescents and young adults. Timely diagnosis and intervention are keys to saving the affected testicle. This review presents current trends in the diagnosis and treatment of torsion, potential pitfalls and consequent outcomes. Additionally, other salient issues surrounding testicular torsion are also discussed, including: pathogenesis of injury, legal ramifications, fertility outcomes, novel management techniques, and recent advances in diagnostic technology., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease., (Copyright © 2018 by the National Comprehensive Cancer Network.)

The Ofunato Bay in Iwate Prefecture, Japan is a deep coastal bay located at the center of the Sanriku Rias Coast and considered an economically and environmentally important asset. Here, we describe the first whole genome sequencing (WGS) study on the microbial community of the bay, where surface water samples were collected from three stations along its length to cover the entire bay; we preliminarily sequenced a 0.2 μm filter fraction among sequentially size-fractionated samples of 20.0, 5.0, 0.8 and 0.2 μm filters, targeting the free-living fraction only. From the 0.27-0.34 Gb WGS library, 0.9 × 10 6 -1.2 × 10 6 reads from three sampling stations revealed 29 bacterial phyla (~80% of assigned reads), 3 archaeal phyla (~4%) and 59 eukaryotic phyla (~15%). Microbial diversity obtained from the WGS approach was compared with 16S rRNA gene results by mining WGS metagenomes, and we found similar estimates. The most frequently recovered bacterial sequences were Proteobacteria, predominantly comprised of 18.0-19.6% Planktomarina (Family Rhodobacteraceae) and 13.7-17.5% Candidatus Pelagibacter (Family Pelagibacterales). Other dominant bacterial genera, including Polaribacter (3.5-6.1%), Flavobacterium (1.8-2.6%), Sphingobacterium (1.4-1.6%) and Cellulophaga (1.4-2.0%), were members of Bacteroidetes and likely associated with the degradation and turnover of organic matter. The Marine Group I Archaea Nitrosopumilus was also detected. Remarkably, eukaryotic green alga Bathycoccus, Ostreococcus and Micromonas accounted for 8.8-15.2%, 3.6-4.9% and 2.1-3.1% of total read counts, respectively, highlighting their potential roles in the phytoplankton bloom after winter mixing., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ofunato Bay, in Japan, is the home of buoy-and-rope-type oyster aquaculture activities. Since the oysters filter suspended materials and excrete organic matters into the seawater, bacterial communities residing in its vicinity may show dynamic changes depending on the oyster culture activities. We employed a shotgun metagenomic technique to study bacterial communities near oyster aquaculture facilities at the center of the bay (KSt. 2) and compared the results with those of two other localities far from the station, one to the northeast (innermost bay, KSt. 1) and the other to the southwest (bay entrance, KSt. 3). Seawater samples were collected every month from January to December 2015 from the surface (1 m) and deeper (8 or 10 m) layers of the three locations, and the sequentially filtered fraction on 0.2-μm membranes was sequenced on an Illumina MiSeq system. The acquired reads were uploaded to MG-RAST for KEGG functional abundance analysis, while taxonomic analyses at the phylum and genus levels were performed using MEGAN after parsing the BLAST output. Discrimination analyses were then performed using the ROC-AUC value of the cross validation, targeting the depth (shallow or deep), locality [(KSt. 1 + KSt. 2) vs. KSt 3; (KSt. 1 + KSt. 3) vs. KSt. 2 or the (KSt. 2 + KSt. 3) vs. KSt. 1] and seasonality (12 months). The matrix discrimination analysis on the adjacent 2 continuous seasons by ROC-AUC, which was based on the datasets that originated from different depths, localities and months, showed the strongest discrimination signal on the taxonomy matrix at the phylum level for the datasets from July to August compared with those from September to June, while the KEGG matrix showed the strongest signal for the datasets from March to June compared with those from July to February. Then, the locality combination was subjected to the same ROC-AUC discrimination analysis, resulting in significant differences between KSt. 2 and KSt. 1 + KSt. 3 on the KEGG matrix. These results suggest that aquaculture activities markedly affect bacterial functions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Ofunato Bay in the northeastern Pacific Ocean area of Japan possesses the highest biodiversity of marine organisms in the world and has attracted much attention due to its economic and environmental importance. We report here a shotgun metagenomic analysis of the year-round variation in free-living bacterioplankton collected across the entire length of the bay. Phylogenetic differences among spring, summer, autumn and winter bacterioplankton suggested that members of Proteobacteria tended to decrease at high water temperatures and increase at low temperatures. It was revealed that Candidatus Pelagibacter varied seasonally, reaching as much as 60% of all sequences at the genus level in the surface waters during winter. This increase was more evident in the deeper waters, where they reached up to 75%. The relative abundance of Planktomarina also rose during winter and fell during summer. A significant component of the winter bacterioplankton community was Archaea (mainly represented by Nitrosopumilus), as their relative abundance was very low during spring and summer but high during winter. In contrast, Actinobacteria and Cyanobacteria appeared to be higher in abundance during high-temperature periods. It was also revealed that Bacteroidetes constituted a significant component of the summer bacterioplankton community, being the second largest bacterial phylum detected in the Ofunato Bay. Its members, notably Polaribacter and Flavobacterium, were found to be high in abundance during spring and summer, particularly in the surface waters. Principal component analysis and hierarchal clustering analyses showed that the bacterial communities in the Ofunato Bay changed seasonally, likely caused by the levels of organic matter, which would be deeply mixed with surface runoff in the winter., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ofunato Bay is located in the northeastern Pacific Ocean area of Japan, and it has the highest biodiversity of marine organisms in the world, primarily due to tidal influences from the cold Oyashio and warm Kuroshio Currents. Our previous results from performing shotgun metagenomics indicated that Candidatus Pelagibacter ubique and Planktomarina temperata were the dominant bacteria (Reza et al., 2018a, 2018b). These bacteria are reportedly able to catabolize dimethylsulfoniopropionate (DMSP) produced from phytoplankton into dimethyl sulfide (DMS) or methanethiol (MeSH). This study was focused on seasonal changes in the abundances of bacterial genes (dddP, dmdA) related to DMSP catabolism in the seawater of Ofunato Bay by BLAST+ analysis using shotgun metagenomic datasets. We found seasonal changes among the Candidatus Pelagibacter ubique strains, including those of the HTCC1062 type and the Red Sea type. A good correlation was observed between the chlorophyll a concentrations and the abundances of the catabolic genes, suggesting that the bacteria directly interact with phytoplankton in the marine material cycle system and play important roles in producing DMS and MeSH from DMSP as signaling molecules for the possible formation of the scent of the tidewater or as fish attractants., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Shrimps inhabiting coastal waters can survive in a wide range of salinity. However, the molecular mechanisms involved in their acclimation to different environmental salinities have remained largely unknown. In the present study, we acclimated kuruma shrimp ( Marsupenaeus japonicus ) at 1.7%, 3.4% and 4.0% salinities. After acclimating for 6, 12, 24 and 72 h, we determined free amino acid concentrations in their abdominal muscle, and performed RNA sequencing analysis on this muscle. The concentrations of free amino acids were clearly altered depending on salinity after 24 h of acclimation. Glutamine and alanine concentrations were markedly increased following the increase of salinity. In association with such changes, many genes related to amino acid metabolism changed their expression levels. In particular, the increase of the expression level of the gene encoding glutamate-ammonia ligase, which functions in glutamine metabolism, appeared to be associated with the increased glutamine concentration at high salinity. Furthermore, the increased alanine concentration at high salinity was likely associated with the decrease in the expression levels of the the gene encoding alanine-glyoxylate transaminase. Thus, there is a possibility that changes in the concentration of free amino acids for osmoregulation in kuruma shrimp are regulated by changes in the expression levels of genes related to amino acid metabolism., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Antisperm antibodies potentially inhibit sperm functions causing the sterility in humans and experimentally treated animals. However, there is no information about antisperm antibodies emerging spontaneously in wildlife. In this study, we searched for the sperm-reactive antibodies, spontaneously produced in wild sika deer (Cervus nippon), and identified the sperm antigens. We collected 529 fecal masses of sika deer in Japanese cities, from which we extracted the mucosal antibodies to test them for reactivities to deer sperm proteins by ELISA. Two of the extracts contained IgAs that were highly reactive to the sperm proteins. The molecular weights of the active IgAs, partially purified by DEAE-sephadex A-50, were estimated at more than 100 kDa, suggesting that the IgAs evaded drastic digestion in the gastrointestinal tract. Two-dimensional electrophoresis and immunoblotting detected three major antigens, and the following LC-MS/MS analysis identified them as alpha-enolase, phosphoglycerate kinase 2 and acrosin-binding protein. The antibodies were cross-reactive to a recombinant human acrosin-binding protein. To our knowledge, this is the first research to find that the sperm-reactive antibodies are produced spontaneously in wildlife and they recognize a common antigen found in humans.

Objectives: We tested cytoplasmic HuR (cHuR) as a predictive marker for response to chemotherapy by examining tumor samples from the international European Study Group of Pancreatic Cancer-3 trial, in which patients with resected pancreatic ductal adenocarcinoma (PDA) received either gemcitabine (GEM) or 5-fluorouracil (5-FU) adjuvant monotherapy., Background: Previous studies have implicated the mRNA-binding protein, HuR (ELAVL1), as a predictive marker for PDA treatment response in the adjuvant setting. These studies were, however, based on small cohorts of patients outside of a clinical trial, or a clinical trial in which patients received multimodality therapy with concomitant radiation., Methods: Tissue samples from 379 patients with PDA enrolled in the European Study Group of Pancreatic Cancer-3 trial were immunolabeled with an anti-HuR antibody and scored for cHuR expression. Patients were dichotomized into groups of high versus low cHuR expression., Results: There was no association between cHuR expression and prognosis in the overall cohort [disease-free survival (DFS), P = 0.44; overall survival, P = 0.41). Median DFS for patients with high cHuR was significantly greater for patients treated with 5-FU compared to GEM [20.1 months, confidence interval (CI): 8.3-36.4 vs 10.9 months, CI: 7.5-14.2; P = 0.04]. Median DFS was similar between the treatment arms in patients with low cHuR (5-FU, 12.8 months, CI: 10.6-14.6 vs GEM, 12.9 months, CI: 11.2-15.4)., Conclusions: Patients with high cHuR-expressing tumors may benefit from 5-FU-based adjuvant therapy as compared to GEM, whereas those patients with low cHuR appear to have no survival advantage with GEM compared with 5-FU. Further studies are needed to validate HuR as a biomarker in both future monotherapy and multiagent regimens.