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Background: Investigating prevalence of child abuse in sport is a relatively new field of research, born from the need for credible data on this phenomenon., Objective: To establish prevalence rates of interpersonal violence against children in sport in six European countries., Participants and Setting: The sample (N = 10,302) consists of individuals aged 18-30 who had participated in organized sport prior to age 18 (49.3 % male, 50 % female)., Methods: A self-report questionnaire was developed (the Interpersonal Violence Against Children in Sport Questionnaire or IVACS-Q) to measure prevalence of five categories of interpersonal violence (neglect, psychological violence, physical violence, non-contact sexual violence, and contact sexual violence) against children who participate in sport. Validation testing (published separately) showed reasonable levels of convergent and divergent validity. Prevalence rates are calculated by national context, whether inside or outside sport, and by sex (male/female)., Results: Prevalence of IVACS inside sport differed by category: psychological violence (65 %, n = 6679), physical violence (44 %, n = 4514), neglect (37 %, n = 3796), non-contact sexual violence (35 %, n = 3565), and contact sexual violence (20 %, n = 2060). Relatively small geographical differences were found. Across all categories, males (79 %, n = 4018) reported significantly more experiences inside sport than females (71 %, n = 3653) (χ 2 (1) = 92.507, p < .000). Strong correlations were found between experiencing violence inside and outside sport., Conclusions: Interpersonal violence against children in sport is widespread. The sector's approach to prevention must recognize the risks to female and male children (and all children) and the additional vulnerabilities of abused children. Further comparative and longitudinal research within sport is required., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: As long-term survival of pediatric liver transplant recipients increases, the assessment of physical, psychological, and social well-being becomes more important., Methods: In this retrospective analysis, 120 young adult patients (age ≥18 y) who underwent liver transplantation in childhood were studied. Patients with ideal outcome were defined as patients with perfect graft function, with no complications from the immunosuppressive medication, no late retransplantation, and no steroid treatment. Also, the patients' drug adherence and their psychosocial situation were assessed., Results: After a median follow-up of 19 y, only 16.7% of the patients (mean age: 26.5 y) were considered patients with ideal outcome. The main reasons precluding ideal outcome were chronic kidney disease (38.3%), elevated liver enzymes (33.3%), and arterial hypertension (31.7%). Ideal outcome decreased over time from 54% to 42%, 26%, and 8% at 10-, 15-, 20-, and 25-y follow-up, respectively. Reduced drug adherence was noted in 24.8% of patients and associated with a significantly higher prevalence of donor-specific antibodies class II ( P  = 0.015), elevated transaminases ( P  = 0.010), and chronic rejection ( P  < 0.001). Also, 15% of patients had a psychiatric disease, mainly depression., Conclusions: The morbidity of young adults who underwent liver transplantation as children was high and increased over time. The majority developed complications from immunosuppression or chronic graft dysfunction. More than 1 in 7 patients had a psychiatric disease and 1 in 4 was not perfectly drug adherent. Therefore, immunosuppressive treatment and psychological care should be optimized for these particularly vulnerable patients., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Distinct niches of the mammalian gut are populated by diverse microbiota, but the contribution of spatial variation to intestinal metabolism remains unclear. Here we present a map of the longitudinal metabolome along the gut of healthy colonized and germ-free male mice. With this map, we reveal a general shift from amino acids in the small intestine to organic acids, vitamins and nucleotides in the large intestine. We compare the metabolic landscapes in colonized versus germ-free mice to disentangle the origin of many metabolites in different niches, which in some cases allows us to infer the underlying processes or identify the producing species. Beyond the known impact of diet on the small intestinal metabolic niche, distinct spatial patterns suggest specific microbial influence on the metabolome in the small intestine. Thus, we present a map of intestinal metabolism and identify metabolite-microbe associations, which provide a basis to connect the spatial occurrence of bioactive compounds to host or microorganism metabolism., (© 2023. The Author(s).)

Purpose: Due to variability in practice patterns when managing patients with facial fractures, the Surgical Infection Society's Therapeutics and Guidelines Committee (SIS) released guidelines in June 2020 concerning antibiotic use in the treatment of patients with facial fractures. The purpose of this study was to measure adherence to SIS guidelines among patients treated for isolated mandibular fractures and to identify factors associated with deviation from SIS guidelines., Materials and Methods: The authors designed and implemented a retrospective cohort study and enrolled a sample derived from the population of patients treated for isolated mandibular fractures at Harborview Medical Center (Seattle, WA) and University of Washington Medical Center-Montlake (Seattle, WA) from June 2020 through October 2021. The primary outcome variable was adherence to SIS antibiotic guidelines (yes or no). Covariates were grouped into the following categories: demographic (age, gender), treatment (operative treatment, primary service, transfer status), and risk factor (Charlson Comorbidity Index, tobacco use, alcohol use, drug use other than marijuana, mandibular injury severity score). Descriptive and bivariate statistics were computed to measure the association between adherence and the study variables. The level of statistical significance was set at a P-value ≤.05., Results: The study sample was composed of 114 patients with a mean age of 41.8 ± 19.0 years and 72% were males. The frequency of adherence to SIS antibiotic protocol was 91.2%. Variables associated with deviation from SIS antibiotic protocol were operative treatment (P-value = .03 - relative risk (RR) not calculable), current drug use other than marijuana (RR = 4.1; 95% confidence interval, 1.3-12.8; P-value = .01), and transfer from an outside facility (RR = 4.1; 95% confidence interval, 1.3-12.8; P-value = .01)., Conclusions: The findings of this study suggest that the SIS antibiotic guidelines in the management of isolated mandible fractures were translated well into practice at our institution as evidenced by the high level of compliance (>90%). To improve adherence, additional research is indicated to better understand how factors such as treatment choice, drug exposure, and transfer status adversely affect adherence to guidelines., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Aim: This study aimed to investigate workplace bullying and explore correlations between bullying, burnout and resilience amongst perioperative nurses in Australia., Background: Workplace bullying in perioperative nursing involves verbal, physical and psychological violence. However, no prior studies have measured Australian perioperative nurses' experiences of workplace bullying nor sought to understand if there is a relationship with burnout and resilience., Methods: A descriptive correlational study was conducted utilizing an online survey incorporating four validated instruments. Descriptive statistics and regression models analysed workplace bullying, burnout and resilience., Results: Over half of perioperative nurses (n = 158/257, 61%) were exposed to workplace bullying. Consequences included fatigue and exhaustion (n = 129/192, 67%), anxiety (n = 123/192, 64%) and sleeplessness (n = 121/192, 63%). Organisational processes (r = .458, p < .001), bullying acts (r = .289, p < .001) and avoidance and withdrawal at work (r = .440, p = .001) increased burnout. Psychosocial distress (r = -.216, p < .001) was associated with decreased resilience., Conclusions: Workplace bullying is a persistent issue with negative impacts upon burnout, resilience and well-being., Implications for Nursing Management: The psychological well-being of employees can be prioritized by establishing and maintaining an organisational climate of psychosocial safety, thereby inhibiting the potential of bullying to manifest and positively influencing employee well-being to help promote workplace engagement, productivity and reduced burnout., (© 2021 John Wiley & Sons Ltd.)

Objective: To establish the extent to which Rugby Union was a compulsory physical education activity in state-funded secondary schools in England and to understand the views of Subject Leaders for Physical Education with respect to injury risk., Method: A cross-sectional research study using data obtained under the Freedom of Information Act (2000) from 288 state-funded secondary schools., Results: Rugby Union was delivered in 81% ( n = 234 of 288) of state-funded secondary school physical education curricula, including 83% ( n = 229 of 275) of state-funded secondary school boys' and 54% ( n = 151 of 282) of girls' physical education curricular. Rugby Union was compulsory in 91% ( n = 208 of 229) of state-funded secondary schools that delivered it as part of the boys' physical education curriculum and 54% ( n = 82 of 151) of state-funded secondary schools that delivered contact Rugby Union as part of the girls' physical education curriculum. Subject Leaders for Physical Education also perceived Rugby Union to have the highest risk of harm of the activities they delivered in their school physical education curriculum., Conclusion: Notwithstanding discussions of appropriate measures (i.e., mandatory concussion training, Rugby Union specific qualifications and CPD) to reduce injury risk, it is recommended that Rugby Union should not be a compulsory activity given that it has a perceived high risk of injury and is an unnecessary risk for children in physical education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 White, Batten, Howarth, Magrath, Piggin, Millward, Parry, Lang, Bullingham, Pearce, Morales, Turner, Humphries, Hardwicke, Anderson, Kirkwood and Pollock.)

Langerhans cell histiocytosis (LCH) is a very rare cause of secondary sclerosing cholangitis. We report the case of a 42-year-old male patient with sclerosing cholangitis and histological evidence of LCH from a bile duct biopsy. Due to rapid disease progression and exhaustion of conservative therapeutic approaches the patient received a liver transplantation. Nearly 2 years after transplantation the patient has a good graft function and no signs of recurrence of the underlying LCH., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Young adults who underwent liver transplantation in childhood (YALTs) are highly vulnerable to non-adherent behavior and psychosocial problems. During the COVID-19 pandemic, special efforts may be necessary to maintain contact with these patients and offer support. This can be achieved through the use of telemedicine. The study's objective was to assess adherence and the psychosocial situation of YALTs during the COVID-19 pandemic in Germany and to evaluate the utilization of video consultations., Methods: In May 2020, a questionnaire was sent to YALTs treated at the Hamburg University Transplant Center, accompanied by the offer of video appointments with the attending physician. The questionnaire included the Generalized Anxiety Disorder Scale 7, the Patient Health Questionnaire 2, and questions compiled by the authors., Results: Of 98 YALTs, 12% used the video consultation, while 65% had an in-person appointment. The 56 patients who completed the questionnaire did not report reduced medication adherence during the pandemic, but 40% missed follow-up visits with their primary care physician or check-up laboratory tests. About 70% of YALTs were afraid to visit their physician and the transplant center, and 34% were afraid of a SARS-CoV-2 infection. Mental health and well-being were unimpaired., Conclusions: During the COVID-19 pandemic, YALTs in our study did not show an increased need for psychosocial support, but a majority were afraid to attend medical appointments, and 40% reported lower appointment adherence. Acceptance of video consultations was lower than expected. The reasons for this need to be further investigated in order to optimize care., (© 2021 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Panfacial trauma refers to high-energy mechanism injuries involving two or more areas of the craniofacial skeleton, the frontal bone, the midface, and the occlusal unit. These can be distracting injuries in an unstable patient and, as in any trauma, Advanced Trauma Life Support (ATLS) protocols should be followed. The airway should be secured, bleeding controlled, and sequential examinations should take place to avoid overlooking injuries. When indicated, neurosurgery and ophthalmology should be consulted as preservation of brain, vision, and hearing function should be prioritized. Once the patient is stabilized, reconstruction aims to reduce panfacial fractures, restore the horizontal and vertical facial buttresses, and resuspend the soft tissue to avoid the appearance of premature aging. Lost or comminuted bone can be replaced with bone grafts, although adequate reduction should be ensured prior to any grafting. Operative sequencing can be performed from top-down and outside-in or from bottom-up and inside-out depending on patient presentation. All protocols can successfully manage panfacial injuries, and the emphasis should be placed on a systematic approach that works from known areas to unknown areas., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Purpose: Our level I trauma center provides care over a large geographic area including Alaska, Washington, Idaho, Montana, and Wyoming, with many patients traveling hundreds of miles to receive care. Distance to a treatment site is documented to be an independent risk factor for complications after multisystem trauma, but it is unclear if it is a risk factor for isolated mandibular fractures. The study purpose was to measure the association between distance to treatment site and risk for postoperative complications after treatment of isolated mandibular fractures., Materials and Methods: The investigators designed and implemented a retrospective cohort study and enrolled a sample derived from patients treated for isolated mandibular fractures at Harborview Medical Center by the oral and maxillofacial surgery service between June 2012 and December 2016. The primary predictor variable was distance (miles) between the patient's residence and site of treatment (Harborview Medical Center). The primary outcome variable was postoperative complication (yes or no), subcategorized as major and minor. Secondary outcome variables were time to treatment between injury and operative treatment (days) and length of hospital stay (LOS) (days). Descriptive, bivariate, and multiple logistic regression statistics were computed to measure the association between distance to treatment site and postoperative complications, time to treatment, and LOS. The level of statistical significance was set at P ≤ .05., Results: The study sample was composed of 403 subjects with a mean age of 32.6 ± 14.3 years and 80% were men. The average distance from the patient's residence to treatment site was 44.8 ± 128.6 miles (range, 0 to 1,440 miles; median, 20.4 miles). Major complications occurred in 11.6% of patients. The average distance between patients with and without postoperative complications was not significantly different (42.3 ± 55.8 miles vs 45.5 ± 141.7 miles; P = .8). Increasing distance was significantly associated with longer LOS (r = 0.16; P < .001) but not time to treatment (r = .04; P = .4)., Conclusions: In contrast to other studies regarding multisystem trauma, complications after treating isolated mandible fractures were not associated with increasing distance to treatment site. Increasing distance may be associated with longer LOS but not time to treatment., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: The purpose of this study was to understand the impact of social distancing policies enacted during the COVID-19 pandemic on the epidemiology of oral and maxillofacial fractures at an urban, Level I trauma center in the United States., Materials and Methods: The investigators designed a retrospective cohort study and enrolled a sample of 883 subjects who presented for evaluation of oral and maxillofacial fractures (OMF) between March 1 and June 30 in the years 2018 through 2020. The primary predictor variable was the evaluation of OMF during a period with social distancing policies (2020 - experimental group) or without social distancing policies in place (2018 or 2019 - control group). The primary outcome variables were the facial fracture diagnosis, the abbreviated injury scale (AIS), injury severity score (ISS), and the mechanism of injury. Appropriate univariate and bivariate statistics were computed, and the level of significance was set at P < .05 for all tests., Results: The number of subjects presenting with OMF was lower during the period of social distancing (n = 235 in 2020) than during the periods without (2018: n = 330; 2019: n = 318). During the period of social distancing, there were more individuals who presented secondary to assault, whereas fewer individuals presented secondary to falls (P = .05). On average, those who presented in 2020 had more severe oral and maxillofacial injuries (mean AIS = 3.2 ± 1.2 in 2020 vs 3.0 ± 1.1 in 2019 and 3.0 ± 1.1 in 2018. P = .03) and more overall injuries (mean ISS = 20.7 ± 13.1 in 2020 vs 19.2 ± 12.5 in 2019; 17.8 ± 12.8 in 2018. P = .03)., Conclusions: The investigators found that during the period of social distancing through the COVID-19 pandemic, the number of OMF cases decreased but that the severity of oral and maxillofacial and overall injuries was higher., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

The impact of renal impairment and hemodialysis on ethyl glucuronide concentrations in hair (hEtG) is not well known. Here, hEtG levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients presenting to the transplant outpatient clinic and compared with the self-reported alcohol consumption in an anonymous validated questionnaire. Estimated daily alcohol intake (EDI) was calculated. A total of 94 patients with varying renal function (Glomerular filtration rate (GFR) > 60 mL/min: group 1 (n = 47); GFR 30-60 ml/min: group 2 (n = 29); GFR < 30 mL/min: group 3 (n = 18)) were included in the study. Fifteen of 18 (83.3%) patients in group 3 were on dialysis. Altogether, hEtG tested positive (> 5 pg/mg) in 25.5% (n = 24) of patients, while 36.2% (n = 34) and 14.9% (n = 14) of patients reported any or regular (> 10 g/d) alcohol consumption, respectively. The median hEtG concentration of positive samples was much higher in patients in group 3 with advanced renal dysfunction or on dialysis than in patients in group 1 or 2 (group 1, 2, 3 dialysis patients: 74, 52, 145 and 155 pg/mg, respectively), although they consumed on average much less alcohol per day (median EDI group 1, 2, 3, dialysis patients: 16, 17, 3 and 3 g/d, respectively). Also, there was a significant correlation between the hEtG concentration and EDI for patients in group 1 (ρ = 0.84; p = 0.01), but not for patients in group 2 (ρ = -0.35, p = 0.39) or 3 (ρ = 0.02, p = 0.96). Furthermore, the ability of hEtG to correctly identify abstainers as such was lower for patients with advanced renal dysfunction than for the remaining patients (specificity for group 1, 2, 3: 92%, 87%, 82%, respectively). So, monitoring hEtG concentration was less reliable in patients with advanced renal dysfunction or on hemodialysis and by far overestimated the amount of alcohol consumed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The management of patients who need chronic and complex care is a focus of attention internationally, brought about by an increase in chronic conditions, requiring significantly more care over longer periods of time. The increase in chronic conditions has placed pressure on health services, financially and physically, bringing about changes in the way care is delivered, with hospital avoidance and home-based care encouraged. In this environment, nurses play an important role in co-ordinating care across services. This review formed one part of a funded project that explored the nurse navigator role within a proposed 24-hour telephone-call service in one regional area that has a diverse population in terms of cultural identity and geographical location in relation to service access., Aim: The review reports on the extant literature on the nurse's role in the provision of afterhours telephone services for patients with chronic and complex conditions. The specific aim was to explore the effectiveness of services for patients in geographically isolated locations., Methods: The methodological approach to the review followed the Preferred Reporting System for Meta-Analyses (PRISMA) guidelines. A thematic analysis was used to identify themes with chronic care models underpinning analysis., Results: Three themes were identified; nurse-led decision making; consumer profile; and program outcomes. Each theme was divided into two sub-themes. The two sub-themes for decision making were: the experience of the staff who provided the service and the tool or protocol used. The two sub-themes for consumers profile were; the geographic/demographic identity of the consumers, and consumer satisfaction. The final theme of outcomes describes how the effectiveness of the service is measured, broken into two sub-themes: the economic/workforce outcomes and the consumer outcomes., Discussion: The provision of an after-hours telephone service, in whatever model used should align with a Chronic Care Model. In this way, after-hours telephone services provided by experienced nurses, supported by ongoing professional development and relevant protocols, form part of the ongoing improvement for chronic and complex care management as a health priority., Competing Interests: The authors have declared that no competing interests exist.

Purpose: In response to the national opioid epidemic crisis, the purpose of this study was to measure changes in opioid and non-narcotic analgesia (NNA) prescribing practices over time after third molar (M3) removal., Materials and Methods: A retrospective double cohort study was utilized enrolling 2 samples of patients who had M3s removed during 2 different 3-month intervals. The primary predictor variable was prescribing practice, divided into cohorts: 1) previous prescribing practice (PPP) occurring early during the evolving opioid epidemic (2014); and 2) current prescribing practice (CPP) (2018). The outcome measures were morphine milligram equivalents (MMEs), NNA prescriptions, and refill MMEs for inadequate pain control (IPC). Other variables were age, gender, payor, provider, anesthesia, procedure, and number of M3s removed. Descriptive, bivariate, and multiple linear and logistic regression models were computed., Results: The sample included 330 subjects with a mean age of 23.1 ± 8.1 years; 42.4% were male. Of the 330 subjects, 147 were in the PPP cohort (44.5%) and 183 in CPP cohort (55.5%). Mean MMEs were 130.1 ± 42.4 and 68.5 ± 32.0 in the PPP and CPP cohorts, respectively (P ≤ .001). An adjusted linear regression model showed differences in MMEs prescribed persisted (P ≤ .001). The frequency of postoperative NNA prescriptions written increased from 2.7 to 71.6% (P ≤ .001). An adjusted logistic regression model also revealed that NNA prescriptions had significantly increased (odds ratio, 242.00; P ≤ .001). No difference was found in the frequency of refills for IPC (P = .13) or mean refill MME prescriptions between the cohorts (P = .48)., Conclusions: Within our academic practice, fewer opioids and more NNAs are being prescribed for postoperative pain after M3 removal without an increase in IPC. Increased awareness through prescribing regulations, non-narcotic research findings, and organizational guidelines could have contributed to these changes., (Copyright © 2019 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Hospitals and other health care providers frequently experience difficulties contacting patients and their carers who live remotely from the town where the health service is located. In 2016 Nurse Navigator positions were introduced into the health services by Queensland Health, to support and navigate the care of people with chronic and complex conditions. One hospital in Far North Queensland initiated an additional free telephone service to provide another means of communication for patients and carers with the NNs and for off-campus health professionals to obtain details about a patient utilising the service. Calls made between 7am and 10pm, seven days per week are answered by a nurse navigator., Aim: To report utilisation of the service by navigated clients and remotely located clinicians compared to use of navigators' individual work numbers and direct health service numbers. We report the reason for calls to the free number and examine features of these calls., Methods: Statistical analysis examined the call reason, duration of calls, setting from where calls originated and stream of calls. Interactions between the reasons for calls and the features of calls, such as contact method, were examined., Results: The major reason for calls was clinical issues and the source of calls was primarily patients and carers. Clinical calls were longer in duration. Shorter calls were mainly non-clinical, made by a health professional. Setting for calls was not related to the reason. The most frequent number used was the individual mobile number of the NN, followed by the hospital landline. Although the free number was utilised by patients and carers, it was not the preferred option., Conclusion: As patients and carers preferred to access their NN directly than via the 1800 number, further research should explore options best suited to this group of patients outside normal business hours., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients with pulpal and periapical conditions often seek treatment for pain, intraoral swelling, or both. Even when definitive, conservative dental treatment (DCDT) is an option, antibiotics are often prescribed. The purpose of this review was to summarize available evidence regarding the effect of antibiotics, either alone or as adjuncts to DCDT, to treat immunocompetent adults with pulpal and periapical conditions, as well as additional population-level harms associated with antibiotic use., Type of Studies Reviewed: The authors updated 2 preexisting systematic reviews to identify newly published randomized controlled trials. They also searched for systematic reviews to inform additional harm outcomes. They conducted searches in MEDLINE, Embase, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature. Pairs of reviewers independently conducted study selection, data extraction, and assessment of risk of bias and certainty in the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach., Results: The authors found no new trials via the update of the preexisting reviews. Ultimately, 3 trials and 8 additional reports proved eligible for this review. Trial estimates for all outcomes suggested both a benefit and harm over 7 days (very low to low certainty evidence). The magnitude of additional harms related to antibiotic use for any condition were potentially large (very low to moderate certainty evidence)., Conclusions and Practical Implications: Evidence for antibiotics, either alone or as adjuncts to DCDT, showed both a benefit and a harm for outcomes of pain and intraoral swelling and a large potential magnitude of effect in regard to additional harm outcomes. The impact of dental antibiotic prescribing requires further research., (Copyright © 2019 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: An expert panel convened by the American Dental Association Council on Scientific Affairs and the Center for Evidence-Based Dentistry conducted a systematic review and formulated clinical recommendations for the urgent management of symptomatic irreversible pulpitis with or without symptomatic apical periodontitis, pulp necrosis and symptomatic apical periodontitis, or pulp necrosis and localized acute apical abscess using antibiotics, either alone or as adjuncts to definitive, conservative dental treatment (DCDT) in immunocompetent adults., Types of Studies Reviewed: The authors conducted a search of the literature in MEDLINE, Embase, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature to retrieve evidence on benefits and harms associated with antibiotic use. The authors used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in the evidence and the Evidence-to-Decision framework., Results: The panel formulated 5 clinical recommendations and 2 good practice statements, each specific to the target conditions, for settings in which DCDT is and is not immediately available. With likely negligible benefits and potentially large harms, the panel recommended against using antibiotics in most clinical scenarios, irrespective of DCDT availability. They recommended antibiotics in patients with systemic involvement (for example, malaise or fever) due to the dental conditions or when the risk of experiencing progression to systemic involvement is high., Conclusion and Practical Implications: Evidence suggests that antibiotics for the target conditions may provide negligible benefits and probably contribute to large harms. The expert panel suggests that antibiotics for target conditions be used only when systemic involvement is present and that immediate DCDT should be prioritized in all cases., (Copyright © 2019 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Purpose: Developing a valid method for assessing mandibular injury severity could permit standardized comparisons of treatment-specific outcomes between and among various mandibular fracture studies. The study purpose was to assess the validity of the Mandible Injury Severity Score (MISS) developed by Shetty et al (J Oral Maxillofac Surg 65:663, 2007) by measuring the association between the MISS and postoperative complications, operative time, and length of hospital stay (LOS) after operative treatment of isolated mandibular fractures., Materials and Methods: The authors designed and implemented a retrospective cohort study and enrolled a sample derived from patients treated for isolated mandibular fractures at Harborview Medical Center (Seattle, WA) by the oral and maxillofacial surgery service from June 2012 through December 2016. The primary predictor variable was the MISS. The primary outcome variable was postoperative complication (yes or no). Secondary outcome variables were operative time and LOS. Descriptive, bivariate, and multiple logistic regression statistics were computed to measure the association between the MISS and postoperative complications. The level of statistical significance was set at a P value less than or equal to .05., Results: The study sample was composed of 415 patients with a mean age of 32.7 ± 14.3 years and 80% were men. The average MISS was 13.4 ± 3.5 (range, 6 to 25). The postoperative complication rate was 21%. The average MISS was significantly higher in patients with postoperative complications than in patients without complications (16.3 ± 3.3 vs 12.6 ± 3.1; P < .001). In the adjusted model, postoperative complications were significantly associated with an increasing MISS (odds ratio [OR] = 1.4; 95% confidence interval [CI], 1.3-1.6; P < .001) and open treatment (OR = 7.6; 95% CI, 1.6-35.6; P = .01). The MISS was positively correlated with operative time (r = 0.529; P < .001) and LOS (r = 0.114; P = .02)., Conclusion: The results of this study suggest that the MISS may be a valid measurement of mandibular injury severity as evidenced by the positive correlation between the MISS and postoperative complications, duration of operation, and LOS., (Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to answer the following clinical question: among patients who have their third molars (M3s) removed, do those who receive only postoperative antibiotics compared with those who receive no perioperative antibiotics have a lower frequency of postoperative inflammatory complications?, Materials and Methods: The authors designed and implemented a prospective cohort study and enrolled a sample of patients who had at least 1 M3 removed in an ambulatory private practice setting from June 2011 through May 2012 by oral and maxillofacial surgeons participating in a practice-based research collaborative. The predictor variable was postoperative antibiotic use categorized as postoperative antibiotics alone or no antibiotics. The primary outcome variable was the presence or absence of an inflammatory complication (ie, alveolar osteitis or surgical site infection) after M3 removal. Descriptive, bivariate, and multiple logistic regression statistics (adjusted for clustering within surgical practices) were computed to measure the association between postoperative antibiotic use alone and inflammatory complications after M3 removal, with statistical significance set at a P value less than or equal to .05., Results: The study sample was composed of 1,877 patients having 5,631 M3s removed, of which 61% received postoperative antibiotics only. The overall inflammatory complication frequencies in the groups receiving postoperative antibiotic only and no antibiotic were 4.3 and 7.5%, respectively (P = .003). After adjusting for differences between the 2 study groups and clustering of patients within surgical practices, postoperative antibiotic use was associated with a 40% decreased risk of developing postoperative inflammatory complications (P = .04) with marginal statistical significance., Conclusions: The results of this study suggest that postoperative antibiotic therapy is associated with a statistically meaningful decreased risk of inflammatory complications after M3 removal compared with no antibiotic therapy., (Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The role of antibiotic use in third molar (M3) surgery is controversial. The purpose of this study was to measure the association between antibiotic use and postoperative inflammatory complications after M3 surgery in the community office-based ambulatory private practice setting., Materials and Methods: The authors designed and implemented a prospective cohort study and enrolled a sample composed of patients who had at least one M3 removed in a private practice setting by oral and maxillofacial surgeons participating in a practice-based research collaborative from June 2011 through May 2012. The predictor variable was antibiotic use of any type, categorized as yes or no. The primary outcome variable was the presence or absence of an inflammatory complication, specifically surgical site infection (SSI) or alveolar osteitis (AO), after M3 removal. Descriptive, bivariate, and multiple logistic regression statistics were computed to measure the association between antibiotic use and inflammatory complications after M3 removal, with statistical significance set at a P value less than or equal to .05., Results: The study sample was composed of 2,954 patients. Three fourths (75.2%) of the sample received antibiotics in some form. The overall inflammatory complication (AO or SSI) frequencies in the antibiotic and nonantibiotic groups were 5.0 and 7.5%, respectively (P = .012). After adjusting for differences between the two groups, statistical significance between the groups persisted., Conclusions: The results of this study suggest that antibiotic therapy, regardless of type, dose, frequency, or pattern of delivery, is associated with a decreased risk of inflammatory complications after M3 removal., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

The threshold photoelectron spectra (TPES) of two unstable nitrogen-containing species, HNCO and NCO, were recorded utilizing vacuum ultraviolet synchrotron radiation. Both are intermediates in combustion processes and play a role in the removal of nitrogen oxides from exhaust gases. The rovibronic structure of the first band in the TPES of HNCO(+) was analyzed within the framework of an orbital ionization model, and the resolved structure of the origin band was assigned to ΔK subbands. An ionization energy of 11.602 ± 0.005 eV was determined and the vibrational structure of the cationic ground state was analyzed by a Franck-Condon fit. Low lying electronically excited states of HNCO(+) were also observed. In a second series of experiments, the NCO radical was generated by flash pyrolysis from chlorine isocyanate. The ionization energy to the X(+) (3)Σ(-) ground state was determined to be 11.76 ± 0.02 eV, while for the a(+) (1)Δ state, a value of 12.93 ± 0.02 eV was obtained. Vibrational structure was observed for both states, and bands were assigned by Franck-Condon simulations.

Threshold photoelectron spectra of combustion relevant C4H5 isomers, 2-butyn-1-yl and 1-butyn-3-yl, and C4H7 isomers, 1-methylallyl and 2-methylallyl, have been recorded using vacuum ultraviolet synchrotron radiation. Adiabatic ionization energies (IEad) have been determined by assigning spectroscopic transitions in mass-selected threshold photoelectron spectra aided by Franck-Condon simulations. The following values were obtained: (7.97 ± 0.02) eV (1-butyn-3-yl), (7.94 ± 0.02) eV (2-butyn-1-yl), (7.48 ± 0.01) eV (1-E-methylallyl), (7.59 ± 0.01) eV (1-Z-methylallyl), and (7.88 ± 0.01) eV (2-methylallyl). Good agreement with CBS-QB3 calculations and simulations could be achieved.

Derivatives of meldrum's acid are known precursors for a number of reactive intermediates. Therefore, we investigate diazomeldrum's acid (DMA) and its pyrolysis products by photoionization using vacuum ultraviolet (VUV) synchrotron radiation. The threshold photoelectron spectrum of DMA yields an ionization energy (IE) of 9.68 eV. Several channels for dissociative photoionization are observed. The first one is associated with loss of CH3, leading to a daughter ion with m/z = 155. Its appearance energy AE0K was determined to be 10.65 eV by fitting the experimental data using statistical theory. A second parallel channel leads to m/z = 69, corresponding to N2CHCO, with an AE0K of 10.72 eV. Several other channels open up at higher energy, among them the formation of acetone cation, a channel expected to be the result of a Wolff-rearrangement (WR) in the cation. When diazomeldrum's acid is heated in a pyrolysis reactor, three thermal decomposition pathways are observed. The major one is well-known and yields acetone, N2 and CO as consequence of the WR. However, two further channels were identified: The formation of 2-diazoethenone, NNCCO, together with acetone and CO2 as the second channel and E-formylketene (OCCHCHCO), propyne, N2 and O2 as a third one. 2-Diazoethenone and E-formylketene were identified based on their threshold photoelectron spectra and accurate ionization energies could be determined. Ionization energies for several isomers of both molecules were also computed. One of the key findings of this study is that acetone is observed upon decomposition of DMA in the neutral as well as in the ion and both point to a Wolff rearrangement to occur. However, the ion is subject to other decomposition channels favored at lower internal energies.

The ionization of two resonantly stabilized radicals, namely 1-phenylpropargyl (1PPR) and 3-phenylpropargyl (3PPR) are reinvestigated applying vacuum ultraviolet synchrotron radiation and threshold photoelectron spectroscopy. Ionization energies of 7.24±0.02 and 7.25±0.01 eV are obtained for 1 and 3PPR respectively, which compare well with ab initio calculations. The quality of the spectra are significantly improved mostly due to the application of a new high-photon-flux grating available at the VUV-beamline of Swiss Light Source. Resolved vibrational features are assigned according to a Franck-Condon approach., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The photoionization and dissociative photoionization of 1,4-di-tert-butyl-1,4-azaborinine by means of synchrotron radiation and threshold photoelectron photoion coincidence spectroscopy is reported. The ionization energy of the compound was determined to be 7.89 eV. Several low-lying electronically excited states in the cation were identified. The various pathways for dissociative photoionization were modeled by statistical theory, and appearance energies AE0K were obtained. The loss of isobutene in a retro-hydroboration reaction is the dominant pathway, which proceeds with a reverse barrier. Pyrolysis of the parent compound in a chemical reactor leads to the generation of several yet unobserved boron compounds. The ionization energies of the C4 H6 BN isomers 1,2- and 1,4-dihydro-1,4-azaborinine and the C3 H6 BN isomer 1,2-dihydro-1,3-azaborole were determined from threshold photoelectron spectra., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently 1-(phenylethynyl)naphthalene (1-PEN) was suggested to be the primary dimerization product of phenylpropargyl radicals and therefore an important polycyclic hydrocarbon in combustion processes. Here we describe a spectroscopic investigation of a genuine 1-PEN sample by several complementary techniques, infrared spectroscopy, multiphoton ionization (MPI), and threshold photoelectron spectroscopy. The infrared spectrum recorded in a gas cell confirms that 1-PEN is indeed the previously observed dimerization product of phenylpropargyl. The origin of the transition into the electronically excited S1 state lies at 30823 cm(-1), as found by MPI. Considerable vibrational activity is observed, and a number of low-wavenumber bands are assigned to a progression in the torsional motion. Values of 6 cm(-1) (S0) and 17 cm(-1) (S1) were derived for the fundamental of the torsion. In the investigated energy range the excited state lifetimes are in the nanosecond range. Spectra of the 1-PEN/Ar cluster exhibit a red shift of the electronic origin of 22 cm(-1), in good agreement with other aromatic molecules. A threshold photoelectron spectrum recorded using synchrotron radiation yields an ionization energy of 7.58 eV for 1-PEN. An excited electronic state of the cation is found at 7.76 eV, and dissociative photoionization does not set in below 15 eV.

Two π-conjugated radicals, fluorenyl (C13H9) and benzhydryl (C13H11), as well as the carbene diphenylmethylene (C13H10) were studied by imaging photoelectron-photoion coincidence spectroscopy using VUV synchrotron radiation. The reactive intermediates were generated by flash pyrolysis from 9-bromofluorene and α-aminodiphenylmethane (adpm), respectively. Adiabatic ionization energies (IEad) for all three species were extracted. Values of 7.01 ± 0.02 eV for fluorenyl and 6.7 ± 0.1 eV for benzhydryl are reported. For the triplet diphenylmethylene, an IEad of 6.8 ± 0.1 eV is found. The dissociative photoionization of 9-bromofluorene, the precursor for fluorenyl, was also studied and modeled with an SSACM approach, yielding an appearance energy AE0K(C13H9(+)/C13H9Br) of 9.4 eV. All experimental values are in very good agreement with computations. For fluorenyl, the IEad agrees well with earlier values, while for the benzhydryl radical, we report a value that is more than 0.6 eV lower than the one previously reported. The geometry change upon ionization is small for all three species. Although individual vibrational bands cannot be resolved, some vibrational transitions in the threshold photoelectron spectrum of fluorenyl are tentatively assigned based on a Franck-Condon simulation. In addition, the dimerization products of fluorenyl and the benzhydryl radical were detected. Ionization energies of (7.69 ± 0.04) and (8.11 ± 0.04) eV were determined for C26H18 and C26H22, respectively. On the basis of the ionization energies, we identified both molecules to be the direct dimerization products, formed in the pyrolysis without further rearrangement. Both dimers might be expected to play a role in soot formation because the radical monomers do appear in flames.

In this paper, we reinvestigate the photoionization of nitrogen containing reactive intermediates of the composition H2CN and H2CNH, molecules of importance in astrochemistry and biofuel combustion. In particular, H2CN is also of considerable interest to theory, because of its complicated potential energy surface. The species were generated by flash pyrolysis, ionized with vacuum ultraviolet synchrotron radiation, and studied by mass-selected threshold photoelectron (TPE) spectroscopy. In the mass-selected TPE-spectrum of m/z = 28, contributions of all four isomers of H2CN were identified. The excitation energy to the triplet cation of the methylene amidogen radical H2CN was determined to be 12.32 eV. Considerable activity in the C-N mode of the cation is visible. Furthermore, we derived values for excitation into the triplet cations of 11.72 eV for cis-HCNH, 12.65 eV for trans-HCNH, and 11.21 eV for H2NC. The latter values are probably accurate to within one vibrational quantum. The spectrum features an additional peak at 10.43 eV that corresponds to excitation into the C(2v)-symmetric H2CN(+). As this structure constitutes a saddle point, the peak is assigned to an activated complex on the singlet potential energy surface of the cation, corresponding to a hydrogen atom migration. For methanimine, H2CNH, the adiabatic ionization energy IE(ad) was determined to be 9.99 eV and the vibrational structure of the spectrum was analyzed in detail. The uncertainty of earlier values that simply assigned the signal onset to the IE(ad) is thus considerably reduced. The spectrum is dominated by the H-N-C bending mode ν1(+) and the rocking mode ν3(+). All experimental data were supported by calculations and Franck-Condon simulations.

We report a synthetic, spectroscopic and computational study of the polycyclic aromatic molecule pyracene, which contains aliphatic five-membered rings annealed to a naphthalene chromophore. An improved route to synthesize the compound is described. Gas-phase IR and solid-state Raman spectra agree with a ground-state D2h structure. The electronically excited S1 A(1)B3u state has been studied by resonance-enhanced multiphoton ionisation. An adiabatic excitation energy T0 = 30,798 cm(-1) (3.818 eV) was determined. SCS-ADC(2) calculations found a D2h minimum energy structure of the S1 state and yielded an excitation energy of +3.98 eV, including correction for zero point vibrational energy. The spectrum shows a rich low-frequency vibrational structure that can be assigned to the overtones of out-of-plane deformation modes of the five-membered rings by comparison with computations. The appearance of these modes as well as the frequency reduction in the excited state indicate that the potential in the S1 state is very flat. At higher excess energies most bands can be assigned to fundamentals, overtones and combination bands of either totally symmetric ag modes or of b2g modes that appear due to vibronic coupling. Lifetimes between 43 ns and 76 ns were measured for a number of vibronic bands. For the S2 state an equilibrium geometry with a non-planar carbon framework was computed. In addition a signal from the pyracene dimer was present. The spectrum shows several broad and structureless transitions. The origin band has a maximum at around 329 nm (30,400 cm(-1)). Again lifetimes between 60 ns and 70 ns were found. The dimer ion signal rises within less than 10 ps. Computations show that a crossed geometry with the long axis of one unit aligned with the short axis of the second constitutes the most stable structure. The broadening of the bands is most likely caused by excimer formation.

Objective: To evaluate the effect of different treatment strategies on enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome., Design: Multicentre retrospective case-control study., Setting: 23 hospitals in northern Germany., Participants: 298 adults with enterohaemorrhagic E coli induced haemolytic uraemic syndrome., Main Outcome Measures: Dialysis, seizures, mechanical ventilation, abdominal surgery owing to perforation of the bowel or bowel necrosis, and death., Results: 160 of the 298 patients (54%) temporarily required dialysis, with only three needing treatment long term. 37 patients (12%) had seizures, 54 (18%) required mechanical ventilation, and 12 (4%) died. No clear benefit was found from use of plasmapheresis or plasmapheresis with glucocorticoids. 67 of the patients were treated with eculizumab, a monoclonal antibody directed against the complement cascade. No short term benefit was detected that could be attributed to this treatment. 52 patients in one centre that used a strategy of aggressive treatment with combined antibiotics had fewer seizures (2% v 15%, P = 0.03), fewer deaths (0% v 5%, p = 0.029), required no abdominal surgery, and excreted E coli for a shorter duration., Conclusions: Enterohaemorrhagic E coli induced haemolytic uraemic syndrome is a severe self limiting acute condition. Our findings question the benefit of eculizumab and of plasmapheresis with or without glucocorticoids. Patients with established haemolytic uraemic syndrome seemed to benefit from antibiotic treatment and this should be investigated in a controlled trial.

The photoionisation of the C(3)H(2) isomer propargylene was studied using synchrotron radiation and coincidence techniques. An adiabatic ionisation energy (IE(ad)) of 8.99 ± 0.02 eV was determined. The precursor diazopropyne was investigated as well. Ionisation and appearance energies were measured., (This journal is © the Owner Societies 2011)

In this Article, we present mass-selected threshold photoelectron spectra of propargyl as well as the 1- and 3-bromopropargyl radicals. The reactive intermediates were produced by flash pyrolysis of suitable precursors and ionized by VUV synchrotron radiation. The TPES of the propargyl radical was simulated using data from a recent high-level computational study. An ionization energy (IE) of 8.71 ± 0.02 eV was obtained, in excellent agreement with computations, but slightly above previous experimental IEs. The pyrolysis of 1,3-dibromopropyne delivers both 1- and 3-bromopropargyl radicals that can be distinguished by their different ionization energies (8.34 and 8.16 eV). To explain the vibrational structure, a Franck-Condon simulation was performed, based on DFT calculations, which can account for all major spectral features. Bromopropargyl photoionizes dissociatively beginning at around 10.1 eV. Cationic excited states of 1- and 3-bromopropargyl were tentatively identified. The dissociative photoionization of the precursor (1,3-dibromopropyne) was also examined, delivering an AE(0K) (C(3)H(2)Br(+)/C(3)H(2)Br(2)) of 10.6 eV.

A novel one-pot method was developed for the preparation of [Ti(η(5)-C(5)H(5))(η(7)-C(7)H(7))] (troticene, 1) by reaction of sodium cyclopentadienide (NaCp) with [TiCl(4)(thf)(2)], followed by reduction of the intermediate [(η(5)-C(5)H(5))(2)TiCl(2)] with magnesium in the presence of cycloheptatriene (C(7)H(8)). The [n]troticenophanes 3 (n=1), 4, 8, 10 (n=2), and 11 (n=3) were synthesized by salt elimination reactions between dilithiated troticene, [Ti(η(5)-C(5)H(4)Li)(η(7)-C(7)H(6)Li)]⋅pmdta (2) (pmdta = N,N',N',N'',N''-pentamethyldiethylenetriamine), and the appropriate organoelement dichlorides Cl(2)Sn(Mes)(2) (Mes = 2,4,6-trimethylphenyl), Cl(2)Sn(2)(tBu)(4), Cl(2)B(2)(NMe(2))(2), Cl(2)Si(2)Me(4), and (ClSiMe(2))(2)CH(2), respectively. Their structural characterization was carried out by single-crystal X-ray diffraction and multinuclear NMR spectroscopy. The stanna[1]- and stanna[2]troticenophanes 3 and 4 represent the first heteroleptic sandwich complexes bearing Sn atoms in the ansa bridge. The reaction of 3 with [Pt(PEt(3))(3)] resulted in regioselective insertion of the [Pt(PEt(3))(2)] fragment into the Sn-C(ipso) bond between the tin atom and the seven-membered ring, which afforded the platinastanna[2]troticenophane 5. Oxidative addition was also observed upon treatment of 4 with elemental sulfur or selenium, to produce the [3]troticenophanes [Ti(η(5)-C(5)H(4)SntBu(2))(η(7)-C(7)H(6)SntBu(2))E] (6: E=S; 7: E=Se). The B-B bond of the bora[2]troticenophane 8 was readily cleaved by reaction with [Pt(PEt(3))(3)] to form the corresponding oxidative addition product [Ti(η(5)-C(5)H(4)BNMe(2))(η(7)-C(7)H(6)BNMe(2))Pt(PEt(3))(2)] (9). The solid-state structures of compounds 5, 6, and 9 were also determined by single-crystal X-ray diffraction., (Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Hyponatremia is one of the most commonly seen electrolyte abnormalities in hospitalized patients. The differential diagnoses are complex once the typical causes for hyponatremia such as congestive cardiac failure, liver failure, hyperglycemia, thiazides, antipsychotic drugs or chemotherapy are excluded. Especially the differentiation between the syndrome of inappropriate ADH secretion and salt-wasting nephropathy as seen in cerebral salt wasting (CSW) can be difficult., Case Report: The case of a 79-year-old lady is discussed who presented to the Emergency Department with extreme dizziness after having fallen off a ladder. Biochemistry studies revealed severe hyponatremia (Na 114 mmol/l) as well as hypochloremia (Cl 85 mmol/l), all other laboratory studies were unremarkable. The intake of a thiazide diuretic, an adrenal insufficiency and other common causes of hyponatremia were excluded. On examination, there were clinical signs of volume depletion. The serum sodium initially improved adequately after the infusion of intravenous normal saline (0.9%) only to fall again along with clinical signs of volume depletion after ceasing the infusion. A high urinary sodium excretion persisted despite hyponatremia and volume depletion. Due to the clinical course the syndrome of inappropriate ADH secretion was considered unlikely and the diagnosis of CSW established. Under therapy with fludrocortisone her sodium stabilized within the normal range and she remained free of symptoms., Conclusion: CSW is an important differential diagnosis of hyponatremia in the hypovolemic patient. It is due to an inadequately high urinary sodium excretion. The response to intravenous normal saline can make the diagnosis likely and distinguish it from SIADH. The exact pathophysiological mechanism behind CSW is not yet completely understood. Therapy consists of fluid and salt supplementation or mineralocorticoid substitution.

In this report, we demonstrate the interaction of the non-structural protein 3 (NS3) of hepatitis C virus (HCV) with alkaloide tropolone (2-hydroxy-2,4,6-heptatriene-1-one) and its derivatives. The compounds were biochemically screened separately against the ATPase and helicase activities of HCV NS3. In the investigations presented, alkaIoide tropolone and its derivatives significantly inhibited the helicase activity of the viral protein when using a DNA substrate, with 50% inhibitory concentration values within a low micromolar range. The results using the RNA substrate were unexpected--none of the tropolone derivatives excerted any modulating influence towards the unwinding activity. Surprisingly, no influence of the nucleoside triphosphatase (NTPase) turnover was observed. Evidence is presented confirming that these compounds do not act by blocking the NTP-binding site, but by occupying an additional allosteric regulatory site. Further mechanisms of action, particularly of some of the derivatives, are discussed.

The use of anabolic substances is prohibited in food-producing animals throughout the European Union. No method is available to reliably detect the misuse of natural hormones in cattle. A method was developed to detect the abuse of testosterone in cattle fattening. Synthesized testosterone is rather depleted in the (13)C/(12)C ratio. Hence, the method is based on gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analysis of urine. To select testosterone metabolites and endogenous reference compounds (ERC), the concentration of urinary steroids of cattle was investigated. Dehydroepiandrosterone and androst-5ene-3beta,17alpha-diol were chosen as ERCs to show endogenous (13)C/(12)C ratios. Etiocholanolone and 5alpha-androstane-3beta,17alpha-diol were chosen as the most important testosterone metabolites. Other metabolites known from literature like epitestosterone were less promising. In principle, GC/C/IRMS is a nonspecific method because finally carbon dioxide is analyzed. Therefore, a dedicated cleanup procedure for the selected steroids was developed. By means of proposed confidence intervals in the isotopic composition of ERCs and metabolites, the administration of testosterone to cattle could be detected reliably. Differences of up to 11 per thousand on the delta-scale between ERC and testosterone metabolites were found after testosterone administration, whereas endogenous differences did not exceed 2 per thousand.

Objective: We aimed to assess the performance of the MicroScan ESBL plus confirmation panel using a series of 87 oxyimino-cephalosporin-resistant Gram-negative bacilli of various species., Methods: Organisms tested included 57 extended-spectrum beta-lactamase (ESBL) strains comprising Enterobacter aerogenes (3), Enterobacter cloacae (10), Escherichia coli (11), Klebsiella pneumoniae (26), Klebsiella oxytoca (3) and Proteus mirabilis (4). Also included were 30 strains resistant to oxyimino cephalosporins but lacking ESBLs, which were characterized with other resistance mechanisms, such as inherent clavulanate susceptibility in Acinetobacter spp. (4), hyperproduction of AmpC enzyme in Citrobacter freundii (2), E. aerogenes (3), E. cloacae (3), E. coli (4), Hafnia alvei (1) and Morganella morganii (1), production of plasmid-mediated AmpC beta-lactamase in K. pneumoniae (3) and E. coli (3) or hyperproduction of K1 enzyme in K. oxytoca (6)., Results: The MicroScan MIC-based clavulanate synergy correctly classified 50 of 57 ESBL strains as ESBL-positive and 23 of 30 non-ESBL strains as ESBL-negative (yielding a sensitivity of 88% and a specificity of 76.7%, respectively). False negatives among ESBL producers were highest with Enterobacter spp. due to masking interactions between ESBL and AmpC beta-lactamases. False-positive classifications occurred in two Acinetobacter spp., one E. coli producing plasmid-mediated AmpC beta-lactamase and two K. oxytoca hyperproducing their chromosomal K1 beta-lactamase., Conclusion: The MicroScan clavulanate synergy test proved to be a valuable tool for ESBL confirmation. However, this test has limitations in detecting ESBLs in Enterobacter spp. and in discriminating ESBL-related resistance from the K1 enzyme and from inherent clavulanate susceptibility in Acinetobacter spp.

5'-O-(4-fluorosulphonylbenzoyl)-esters of ribavirin (FSBR), adenosine (FSBA), guanosine (FSBG) and inosine (FSBI) were obtained by acylation of the 5'-OH of adenosine, guanosine, inosine, and ribavirin with 4-fluorosulphonylbenzoyl chloride (FSBCI) in HMPA. The above derivatives were tested as inhibitors of nucleoside triphosphatase (NTPase)/helicase activities of Flaviviridae: hepatitis C virus (HCV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and dengue virus (DENV) and polymerase activity of HCV and WNV. When the unwinding activity of viral NTPase/helicases was tested under standard conditions, only weak inhibition was obtained with FSBI (IC50 > or = 120 microM) and in the case of FSBG even an activation was seen. The preincubation of the NTPase/helicases with the 5'-O-FSB derivatives increased the inhibitory effect. Screening of the 5'-O-FSB derivatives on inhibition of the WNV and HCV RNA polymerases employing GTP or UTP substrates revealed rather modest inhibitory effect. FSBI exhibited the highest inhibitory activity against WNV (IC50 = 70 microM with UTP substrate) and HCV polymerase (IC50 = 80 microM with GTP substrate). Other 5'-O-FSB derivatives were very weak inhibitors or completely failed to show any activity against HCV and WNV enzymes. In contrast to the NTPase/helicases the preincubation of the polymerases did not influence the inhibition.

Compounds that interact with DNA or RNA generally act as inhibitors of enzymes that unwind DNA or RNA. In the present study we describe the synthesis and properties of some nucleoside analogues that interact with double-stranded DNA but that, in contrast, facilitate the unwinding reaction mediated by West Nile (WN) virus nucleoside triphosphatase (NTPase)/helicase. The nucleoside analogues described, 1-(2'-O-methyl-beta-D-ribofuranosyl)imidazo[4,5-d]pyridazine-4,7(5H,6H)-dione (HMC-HO4), 1-(beta-D-ribofuranosyl)imidazo[4,5-d]pyridazine-4,7(5H,6H)-dione, and 1-(2'-deoxy-alpha-D-ribofuranosyl)imidazo[4,5-d]pyridazine-4,7(5H,6H)dione, all contain the imidazo[4,5-d]pyridazine ring system. The extent of the enhancing effect on helicase activity was found to be dependent on the time of exposure of the DNA substrate to the compounds and their concentrations. The nucleoside analogues were nevertheless found to be capable of uncoupling the ATPase and helicase activities of the enzyme by a mechanism operating on the level of the enzyme. Thus, in the case of HMC-HO4, the direct interaction with the enzyme caused inhibition of its helicase activity, with a half-maximal inhibitory concentration of 30 microM. The similar potency of the compound against replication of WN virus in cell culture suggests that inhibition of the helicase activity of the viral enzyme is responsible for the observed antiviral activity of HMC-HO4 and may indeed represent an important mode of action of antiviral drugs in general. Comparative studies performed with the related NTPase/helicase from hepatitis C virus revealed that the extent of the effects mediated by imidazo[4,5-d]pyridazine nucleosides is enzyme specific. The substances described may represent a starting point for the development of a new class of helicase-specific antivirals.