As one of the most common chronic diseases suffered by adults, periodontitis affects sufferers’ day‐to‐day lives and is a threat to the integrity of the dentition. An important part in the ...condition’s occurrence is played by sociobehavioural factors, the understanding of which is facilitated by using a number of largely complementary theoretical frameworks. Differences among individuals with respect to their periodontal status at any particular point in their life‐course (and particularly once they are into early middle‐age and beyond) are likely to have resulted from prolonged and differential exposure to the various protective and risk factors that determine their periodontal status. Thus, a sound understanding of the psychosocial pathways of the behaviors that are strongly linked to periodontal disease – and how such psychological factors affect the response of the periodontal tissues to pathogens – is essential for improving periodontal health, whether at the personal level or at the population level. Controlling periodontitis in populations therefore requires a number of complementary strategies. The current state of knowledge of its risk factors means that there is sufficient information to enable control of the disease, and public health officials should include it alongside their efforts to control dental caries. Controlling periodontitis has three strategies: (i) a population strategy for altering life practices, particularly those determining smoking behavior and oral self‐care (plaque removal) in the community; (ii) a secondary prevention strategy to detect and treat people with destructive periodontal disease; and (iii) a high‐risk strategy for treating existing disease and preventing further disease in those at special risk. The Common Risk Factor Approach and the health promotion approach are key aspects of these strategies.
Objective
To design clear guidelines for the staging and follow-up of patients with ovarian cancer, and to provide the radiologist with a framework for use in multidisciplinary conferences.
Methods
...Guidelines for ovarian cancer staging and follow-up were defined by the female imaging subcommittee of the ESUR (European Society of Urogenital Radiology) based on the expert consensus of imaging protocols of 12 leading institutions and a critical review of the literature.
Results
Computed tomography (CT) with coverage of the base of the lungs to the inguinal region is regarded as the imaging technique of choice for preoperative staging. Critical diagnostic criteria are presented and the basis for a structured report for preoperative staging is outlined. Following primary treatment for ovarian cancer, clinical assessment and CA-125 are routinely used to monitor patients. For suspected recurrence, CT remains the imaging modality of choice, with positron emission tomography (PET)/CT emerging as the optimal imaging technique for suspected recurrence, particularly in patients with negative CT or magnetic resonance imaging (MRI).
Conclusions
CT is the imaging modality of choice for preoperative staging and detection of recurrence in patients with ovarian cancer.
This article describes the evolution of a Nazarov cyclization-based synthetic strategy targeting the anticancer, antiinflammatory, and insecticidal natural product (±)-rocaglamide. Initial pursuit of ...a polarized heteroaromatic Nazarov cyclization to construct the congested cyclopentane core revealed an unanticipated electronic bias in the pentadienyl cation. This reactivity was harnessed in a successful second-generation approach using an oxidation-initiated Nazarov cyclization of a heteroaryl alkoxyallene. Full details of these two approaches are given, as well as the characterization of undesired reaction pathways available to the Nazarov cyclization product. A sequence of experiments that led to an understanding of the unexpected reactivity of this key intermediate is described, which culminated in the successful total synthesis of (+)-rocaglamide.
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Obesity is intimately associated with diet and dysbiosis of gut microorganisms but anxiolytics, widely used in treatment of psychiatric conditions, frequently result in weight gain ...and associated metabolic disorders. We are interested in effects of the anxiolytic etifoxine, which has not been studied with respect to weight gain or effects on gut microorganisms. Here we induced obesity in mice by feeding a high-fat diet but found that intraperitoneal administration of etifoxine resulted in weight loss and decreased serum cholesterol and triglycerides. Obese mice had increased hepatic transcripts associated with lipid metabolism (cyp7a1, cyp27a1, abcg1 and LXRα) and inflammatory factors (TNFα and IL18) but these effects were reversed after etifoxine treatment other than cyp7a1. Taxonomic profiles of the organisms from the caecum were generated by 16S rRNA gene sequencing and Obese and etifoxine mice show differences by diversity metrics, Differential Abundance and functional metagenomics. Organisms in genus Oscillospira and genera from Lachnospiraceae family and Clostridiales order are higher in Control than Obese and at intermediate levels with etifoxine treatment. With respect to community metabolic potential, etifoxine mice have characteristics similar to Control and particularly with respect to metabolism of butanoate, sphingolipid, lipid biosynthesis and xenobiotic metabolism. We suggest mechanisms where-by etifoxine influences processes of host, such as on bile acid synthesis, and microbiota, such as signalling from production of butanoate and sphingosine, resulting in decreased cholesterol, lipids and inflammatory factors. We speculate that the indirect effect of etifoxine on microbial composition is mediated by microbial β-glucuronidases that metabolise excreted etifoxine glucuronides.
We examined demographic and socioeconomic differences in the consumption of sugar-sweetened beverages (SSBs), its association with dental caries in children, and whether exposure to water ...fluoridation modifies this association.
In a cross-sectional study, we used a stratified, clustered sampling design to obtain information on 16 508 children aged 5 to 16 years enrolled in Australian school dental services in 2002 to 2005. Dental staff assessed dental caries, and parents completed a questionnaire about their child's residential history, sources of drinking water, toothbrushing frequency, socioeconomic status (SES), and SSB consumption.
Children who brushed their teeth less often and were older, male, of low SES, from rural or remote areas consumed significantly more SSBs. Caries was significantly associated with greater SSB consumption after controlling for potential confounders. Finally, greater exposure to fluoridated water significantly reduced the association between children's SSB consumption and dental caries.
Consumption of SSBs should be considered a major risk factor for dental caries. However, increased exposure to fluoridated public water helped ameliorate the association between SSB consumption and dental decay. These results reconfirm the benefits of community water fluoridation for oral health.
Seaweed and seagrass communities in the northeast Atlantic have been profoundly impacted by humans, and the rate of change is accelerating rapidly due to runaway CO2 emissions and mounting pressures ...on coastlines associated with human population growth and increased consumption of finite resources. Here, we predict how rapid warming and acidification are likely to affect benthic flora and coastal ecosystems of the northeast Atlantic in this century, based on global evidence from the literature as interpreted by the collective knowledge of the authorship. We predict that warming will kill off kelp forests in the south and that ocean acidification will remove maerl habitat in the north. Seagrasses will proliferate, and associated epiphytes switch from calcified algae to diatoms and filamentous species. Invasive species will thrive in niches liberated by loss of native species and spread via exponential development of artificial marine structures. Combined impacts of seawater warming, ocean acidification, and increased storminess may replace structurally diverse seaweed canopies, with associated calcified and noncalcified flora, with simple habitats dominated by noncalcified, turf‐forming seaweeds.
In this study, predictions are made as to how rapid warming and ocean acidification are likely to affect benthic flora and coastal ecosystems of the north‐east Atlantic in this century based on global evidence from the literature as interpreted by the collective knowledge of the authorship. We predict that kelp forests will die out in the south due to warming, maerl habitat lost in the north through acidification, seagrasses will proliferate, associated epiphytes will switch from calcified algae to diatoms and filamentous species, and invasive species will thrive. Thus, structurally diverse seaweed canopies with associated calcified and noncalcified flora may be replaced with simple habitats dominated by noncalcified, turf‐forming seaweeds.
Periodontal diseases are some of the major oral diseases and conditions in adults.
Objective
The study aimed to present the population patterns of periodontal diseases and trends of periodontitis in ...the Australian adult population.
Methods
Data collected in the recent National Study of Adult Oral Health (NSAOH) 2017–18 were used to present the current population patterns of periodontal diseases. Periodontal assessment was carried out at three sites per tooth for all present teeth, excluding third molars. Prevalence of gingivitis, periodontal pocket depth of 4+ mm, gingival recession of 2+ mm, and clinical attachment loss of 4+ mm were calculated and reported. The US CDC/AAP case definition was used to define cases of moderate to severe periodontitis. NSAOH 2017–18 data were combined with data collected in NSAOH 2004–06 using similar methods to describe age‐ and cohort‐related trends of periodontitis.
Results
The prevalence of periodontal diseases and conditions were relatively high in the Australian adult population. Some three in every ten Australian adults had moderate to severe periodontitis. There was a tendency of higher prevalence of periodontitis in NSAOH 2017–18 than in NSAOH 2004–06 among people of the same age.
Conclusion
Periodontal diseases and conditions remain a significant problem in the Australian adult population.
Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma have high survival when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with ...cetuximab—an antibody against the epidermal growth factor receptor—can preserve high survival and reduce treatment toxicity is unknown. We investigated whether cetuximab would maintain a high proportion of patient survival and reduce acute and late toxicity.
RTOG 1016 was a randomised, multicentre, non-inferiority trial at 182 health-care centres in the USA and Canada. Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma; American Joint Committee on Cancer 7th edition clinical categories T1–T2, N2a–N3 M0 or T3–T4, N0–N3 M0; Zubrod performance status 0 or 1; age at least 18 years; and adequate bone marrow, hepatic, and renal function. We randomly assigned patients (1:1) to receive either radiotherapy plus cetuximab or radiotherapy plus cisplatin. Randomisation was balanced by using randomly permuted blocks, and patients were stratified by T category (T1–T2 vs T3–T4), N category (N0–N2a vs N2b–N3), Zubrod performance status (0 vs 1), and tobacco smoking history (≤10 pack-years vs >10 pack-years). Patients were assigned to receive either intravenous cetuximab at a loading dose of 400 mg/m2 5–7 days before radiotherapy initiation, followed by cetuximab 250 mg/m2 weekly for seven doses (total 2150 mg/m2), or cisplatin 100 mg/m2 on days 1 and 22 of radiotherapy (total 200 mg/m2). All patients received accelerated intensity-modulated radiotherapy delivered at 70 Gy in 35 fractions over 6 weeks at six fractions per week (with two fractions given on one day, at least 6 h apart). The primary endpoint was overall survival, defined as time from randomisation to death from any cause, with non-inferiority margin 1·45. Primary analysis was based on the modified intention-to-treat approach, whereby all patients meeting eligibility criteria are included. This study is registered with ClinicalTrials.gov, number NCT01302834.
Between June 9, 2011, and July 31, 2014, 987 patients were enrolled, of whom 849 were randomly assigned to receive radiotherapy plus cetuximab (n=425) or radiotherapy plus cisplatin (n=424). 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were subsequently eligible. After median follow-up duration of 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criteria for overall survival (hazard ratio HR 1·45, one-sided 95% upper CI 1·94; p=0·5056 for non-inferiority; one-sided log-rank p=0·0163). Estimated 5-year overall survival was 77·9% (95% CI 73·4–82·5) in the cetuximab group versus 84·6% (80·6–88·6) in the cisplatin group. Progression-free survival was significantly lower in the cetuximab group compared with the cisplatin group (HR 1·72, 95% CI 1·29–2·29; p=0·0002; 5-year progression-free survival 67·3%, 95% CI 62·4–72·2 vs 78·4%, 73·8–83·0), and locoregional failure was significantly higher in the cetuximab group compared with the cisplatin group (HR 2·05, 95% CI 1·35–3·10; 5-year proportions 17·3%, 95% CI 13·7–21·4 vs 9·9%, 6·9–13·6). Proportions of acute moderate to severe toxicity (77·4%, 95% CI 73·0–81·5 vs 81·7%, 77·5–85·3; p=0·1586) and late moderate to severe toxicity (16·5%, 95% CI 12·9–20·7 vs 20·4%, 16·4–24·8; p=0·1904) were similar between the cetuximab and cisplatin groups.
For patients with HPV-positive oropharyngeal carcinoma, radiotherapy plus cetuximab showed inferior overall survival and progression-free survival compared with radiotherapy plus cisplatin. Radiotherapy plus cisplatin is the standard of care for eligible patients with HPV-positive oropharyngeal carcinoma.
National Cancer Institute USA, Eli Lilly, and The Oral Cancer Foundation.
Background
Radiation Therapy Oncology Group (RTOG)‐0129 recursive partitioning analysis was the basis for risk‐based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors’ ...knowledge, the question of whether RTOG‐0129 overall survival (OS) estimates for low‐risk, intermediate‐risk, and high‐risk groups are similar in other data sets or applicable to progression‐free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG‐0129 risk groups persist at 5 years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups.
Methods
Prospective randomized clinical trials were analyzed retrospectively. RTOG‐0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG‐0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible.
Results
There was a total of 260 patients and 287 patients, respectively, from RTOG‐0129 and RTOG‐0522, with median follow‐ups for surviving patients of 7.9 years (range, 1.7‐9.9 years) and 4.7 years (range, 0.1‐7.0 years), respectively. Previous OS differences in RTOG‐0129 persisted at 5 years. In RTOG‐0522, the 5‐year OS rates for the low‐risk, intermediate‐risk, and high‐risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5‐year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG‐0522 among a subgroup of patients considered to be at very good risk (p16‐positive disease, smoking history of ≤10 pack‐years, and classified with T1‐T2 disease with ipsilateral lymph nodes measuring ≤6 cm or T3 disease without contralateral or >6 cm lymph nodes), the 5‐year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group.
Conclusions
RTOG‐0129 risk groups persisted at 5 years and were reproducible in RTOG‐0522. However, there was variability in the estimates. These data underscore the importance of long‐term follow‐up and appropriate patient selection in therapeutic deintensification trials.
To the authors’ knowledge, the issue of whether Radiation Therapy Oncology Group (RTOG)‐0129 overall survival estimates for low‐risk, intermediate‐risk, and high‐risk groups are similar in other data sets or applicable to progression‐free survival is unknown. In the current study, RTOG‐0129 risk groups appear to persist at 5 years, are reproducible in RTOG‐0522, and can be applied to progression‐free survival. However, there is variability in the estimates, which underscores the importance of long‐term follow‐up in therapeutic deintensification.
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