Effect of composite type and placement technique on cuspal strain

Abstract

Objective

To compare the cuspal strain in Class II restorations made with bulk-fill and conventional composite resins.

Materials and methods

Fifty extracted maxillary premolars were mounted into phenolic rings and divided into five groups (n = 10). Specimens received standardized MOD preparations. A two-step self-etch adhesive was applied and the preparations were restored using a custom matrix as follows: Filtek Supreme Ultra in eight 2-mm increments (FSUI); Filtek Supreme Ultra in bulk (FSUB); SonicFill in bulk (SF); SureFil SDR flow in bulk, covered with a 2-mm occlusal layer of Filtek Supreme Ultra (SDR/FSU); Tetric EvoCeram Bulk Fill in bulk (TEBF). Strain gages bonded to the buccal and lingual cusps recorded cuspal strain during restorations. End strain values were determined and data were subjected to Kruskal-Wallis testing, followed by one-way ANOVA and Tukey´s post hoc test.

Results

Combined strain values and standard deviations (in µɛ) were: FSUI: 723 ± 102.8, FSUB: 929.2 ± 571.9, SF: 519.1 ± 80.2, SDR-FSU: 497.4 ± 67.6 and TEBF: 604.5 ± 127.1. A significant difference was found between group FSUI and groups SF, SDR-FSU, and TEBF. Group FSUB showed significantly higher mean strain and greater standard deviation than all other groups due to cuspal fractures, and was thus excluded from the statistical analysis.

Conclusions

The tested bulk-fill composite resins exerted less strain onto tooth structure than the incrementally placed conventional composite resin, although the magnitude of generated strain was product-dependent. Bulk-filling with conventional composite resins is contraindicated.

Clinical significance

Bulk-fill composite resins exerted less strain onto adjacent tooth structure than a traditional composite, even when that composite is was placed incrementally. Bulk-filling with traditional composite resins is unpredictable and contraindicated.

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Activation of professional and personal network relations when experiencing a symptom: a population-based cross-sectional study

Objective

To describe patterns of disclosure of symptoms experienced among people in the general population to persons in their personal and/or professional network.

Design

A population-based cross-sectional study. Data were collected from a web-based survey.

Setting

The general population in Denmark.

Participants

100 000 individuals randomly selected, representative of the adult Danish population aged ≥20 years were invited. Approximately 5% were not eligible for inclusion. 49 706 (men=23 240; women=26 466) of 95 253 eligible individuals completed the questionnaire; yielding a response rate of 52.2%. Individuals completing all questions regarding social network relations form the study base (n=44 313).

Primary and secondary outcome measures

Activation of personal and/or professional relations when experiencing a symptom.

Results

The 44 313 individuals reported in total 260 079 symptom experiences within the last 4 weeks. No professional network relation was used in two-thirds of all reported symptoms. The general practitioner (GP) was the most frequently reported professional relation activated (22.5%). People reporting to have available personal relations were slightly less inclined to contact the GP (21.9%) when experiencing a symptom compared with people with no reported personal relations (26.8%). The most commonly activated personal relations were spouse/partner (56.4%) and friend (19.6%). More than a quarter of all reported symptom experiences was not shared with anyone, personal nor professional. The symptom experiences with the lowest frequency of network activation were symptoms such as black stool, constipation, change in stool texture and frequent urination.

Conclusion

This study emphasises variation in the activation of network relations when experiencing a symptom. Symptoms were shared with both personal and professional relations, but different patterns of disclosures were discovered. For symptoms derived from the urogenital or colorectal region, the use of both personal and professional relations was relatively small, which might indicate reticence to involve other people when experiencing symptoms of that nature.

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Effects of school-based intervention by emergency medical technicians on students and their parents: a community-based prospective study of the Akashi project

Objective

Stroke lessons for youth provided by emergency medical technicians (EMTs) may be an effective strategy to facilitate early intervention for patients with stroke. The aim of this study was to examine how effective EMT-led lessons on stroke awareness for schoolchildren were at disseminating stroke information.

Setting, participants and outcome measures

The study was performed in the city of Akashi, Hyogo, Japan (Akashi project). Children (aged 9–10 years old) at 11 public elementary schools and their parents were enrolled in this study. EMTs from the firefighting headquarters provided lessons on stroke to the children using our educational materials between September 2014 and October 2015. Each child was given our educational materials to take home and discuss stroke with their parents. The children and their parents answered questionnaires on stroke knowledge before, immediately and at 3 months after the lesson.

Results

A total of 763 children and 489 parents were enrolled (ie, 64% of children). The scores of either stroke symptoms or risk factors were significantly higher immediately and at 3 months after the lesson, compared with before the lesson, both in children and the parents (p<0.01). Compared with the baseline in both groups (58% in children, 83% in parents), the meaning of the FAST mnemonic at 3 months (88%, 94%), as well as at immediately after the lesson (90%, 89%), was significantly higher (p<0.001).

Conclusion

Stroke education by EMTs was effective in increasing stroke awareness in elementary school children, as well as their parents.

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Sociodemographic variations in the amount, duration and cost of potentially preventable hospitalisation for chronic conditions among Aboriginal and non-Aboriginal Australians: a period prevalence study of linked public hospital data

Objectives

To determine disparities in rates, length of stay (LOS) and hospital costs of potentially preventable hospitalisations (PPH) for selected chronic conditions among Aboriginal and non-Aboriginal South Australians (SA), then examine associations with area-level socioeconomic disadvantage and remoteness.

Setting

Period prevalence study using linked, administrative public hospital records.

Participants

Participants included all SA residents in 2005–2006 to 2010–2011. Analysis focused on those individuals experiencing chronic PPH as defined by the Australian Institute of Health and Welfare.

Primary outcome measures

Number and rates (unadjusted, then adjusted for sex and age) of chronic PPH, total LOS and direct hospital costs by Aboriginality.

Results

Aboriginal SAs experienced higher risk of index chronic PPH compared with non-Aboriginals (11.5 and 6.2 per 1000 persons per year, respectively) and at younger ages (median age 48 vs 70 years). Once hospitalised, Aboriginal people experienced more chronic PPH events, longer total LOS with higher costs than non-Aboriginal people (2.6 vs 1.9 PPH per person; 11.7 vs 9.0 days LOS; at $A17 928 vs $A11 515, respectively). Compared with population average LOS, the standardised rate ratio of LOS among Aboriginal people increased by 0.03 (95% CI 0.00 to 0.07) as disadvantage rank increased and 1.04 (95% CI 0.63 to 1.44) as remoteness increased. Non-Aboriginal LOS also increased as disadvantage increased but at a lower rate (0.01 (95% CI 0.01 to 0.01)). Costs of Aboriginal chronic PPH increased by 0.02 (95% CI 0.00 to 0.06) for each increase in disadvantage and 1.18 (95% CI 0.80 to 1.55) for increased remoteness. Non-Aboriginal costs also increased as disadvantage increased but at lower rates (0.01 (95% CI 0.01 to 0.01)).

Conclusion

Aboriginal people's heightened risk of chronic PPH resulted in more time in hospital and greater cost. Systematic disparities in chronic PPH by Aboriginality, area disadvantage and remoteness highlight the need for improved uptake of effective primary care. Routine, regional reporting will help monitor progress in meeting these population needs.

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Appropriateness of cases presenting in the emergency department following ambulance service secondary telephone triage: a retrospective cohort study

Objective

To investigate the appropriateness of cases presenting to the emergency department (ED) following ambulance-based secondary telephone triage.

Design

A pragmatic retrospective cohort analysis of all the planned and unplanned ED presentations within 48 hours of a secondary telephone triage.

Setting

The secondary telephone triage service, called the Referral Service, and the hospitals were located in metropolitan Melbourne, Australia and operated 24 hours a day, servicing 4.25 million people. The Referral Service provides an in-depth secondary triage of cases classified as low acuity when calling the Australian emergency telephone number.

Population

Cases triaged by the Referral Service between September 2009 and June 2012 were linked to ED and hospital admission records (N=44,523). Planned ED presentations were cases referred to the ED following the secondary triage, unplanned ED presentations were cases that presented despite being referred to alternative care pathways.

Main outcome measures

Appropriateness was measured using an ED suitability definition and hospital admission rates. These were compared with mean population data which consisted of all of the ED presentations for the state (termed the 'average Victorian ED presentation').

Results

Planned ED presentations were more likely to be ED suitable than unplanned ED presentations (OR 1.62; 95% CI 1.5 to 1.7; p<0.001) and the average Victorian ED presentation (OR 1.85; 95% CI 1.01 to 3.4; p=0.046). They were also more likely to be admitted to the hospital than the unplanned ED presentation (OR 1.5; 95% CI 1.4 to 1.6; p<0.001) and the average Victorian ED presentation (OR 2.3, 95% CI 2.24 to 2.33; p<0.001). Just under 15% of cases diverted away from the emergency care pathways presented in the ED (unplanned ED attendances), and 9.5% of all the alternative care pathway cases were classified as ED suitable and 6.5% were admitted to hospital.

Conclusions

Secondary telephone triage was able to appropriately identify many ED suitable cases, and while most cases referred to alternative care pathways did not present in the ED. Further research is required to establish that these were not inappropriately triaged away from the emergency care pathways.

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Protocol for a scoping review to identify and map the global health personnel considered skilled attendants at birth in low and middle-income countries between 2000 and 2015

Introduction

Despite progress towards the Millennium Development Goals (MDG), maternal mortality remains high in countries where there are shortages of skilled personnel able to manage and provide quality care during pregnancy and childbirth. The 'percentage of births attended by skilled health personnel' (SAB, skilled attendants at birth) was a key indicator for tracking progress since the MDGs and is part of the Sustainable Development Goal agenda. However, due to contextual differences between and within countries on the definition of SAB, a lack of clarity exists around the training, competencies, and skills they are qualified to perform. In this paper, we outline a scoping review protocol that poses to identify and map the health personnel considered SAB in low and middle-income countries (LMIC).

Methods and analysis

A search will be conducted for the years 2000–2015 in PubMed/MEDLINE, EMBASE, CINAHL Complete, Cochrane Database of Systematic Reviews, POPLINE and the WHO Global Health Library. A manual search of reference lists from identified studies or systematic reviews and a hand search of the literature from international partner organisations will be done. Original studies conducted in LMIC that assessed health personnel (paid or voluntary) providing interventions during the intrapartum period will be considered for inclusion.

Ethics and dissemination

A scoping review is a secondary analysis of published literature and does not require ethics approval. This scoping review proposes to synthesise data on the training, competency and skills of identified SAB and expands on other efforts to describe this global health workforce. The results will inform recommendations around improved coverage measurement and reporting of SAB moving forward, allowing for more accurate, consistent and timely data able to guide decisions and action around planning and implementation of maternal and newborn health programme globally. Data will be disseminated through a peer-reviewed manuscript, conferences and to key stakeholders within international organisations.

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Barriers and facilitators to healthy lifestyle and acceptability of a dietary and physical activity intervention among African Caribbean prostate cancer survivors in the UK: a qualitative study

Objectives

Diet and lifestyle may have a role in delaying prostate cancer progression, but little is known about the health behaviours of Black British prostate cancer survivors despite this group having a higher prostate cancer mortality rate than their White counterparts. We explored the barriers and facilitators to dietary and lifestyle changes and the acceptability of a diet and physical activity intervention in African Caribbean prostate cancer survivors.

Design

We conducted semistructured in-depth interviews and used thematic analysis to code and group the data.

Participants and setting

We recruited 14 African Caribbean prostate cancer survivors via letter or at oncology follow-up appointments using purposive and convenience sampling.

Results

A prostate cancer diagnosis did not trigger dietary and lifestyle changes in most men. This lack of change was underpinned by five themes: precancer diet and lifestyle, evidence, coping with prostate cancer, ageing, and autonomy. Men perceived their diet and lifestyle to be healthy and were uncertain about the therapeutic benefits of these factors on prostate cancer recurrence. They considered a lifestyle intervention as unnecessary because their prostate-specific antigen (PSA) level was kept under control by the treatments they had received. They believed dietary and lifestyle changes should be self-initiated and motivated, but were willing to make additional changes if they were perceived to be beneficial to health. Nonetheless, some men cited advice from health professionals and social support in coping with prostate cancer as facilitators to positive dietary and lifestyle changes. A prostate cancer diagnosis and ageing also heightened men's awareness of their health, particularly in regards to their body weight.

Conclusions

A dietary and physical activity intervention framed as helping men to regain fitness and aid post-treatment recovery aimed at men with elevated PSA may be appealing and acceptable to African Caribbean prostate cancer survivors.

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Optimising the quality of antibiotic prescribing in out-of-hours primary care in Belgium: a study protocol for an action research project

Introduction

Antimicrobial resistance is a major public health threat driven by inappropriate antibiotic use, mainly in general practice and for respiratory tract infections. In Belgium, the quality of general practitioners' (GPs) antibiotic prescribing is low. To improve antibiotic use, we need a better understanding of this quality problem and corresponding interventions. A general practitioners cooperative (GPC) for out-of-hours (OOH) care presents a unique opportunity to reach a large group of GPs and work on quality improvement. Participatory action research (PAR) is a bottom-up approach that focuses on implementing change into daily practice and has the potential to empower practitioners to produce their own solutions to optimise their antibiotic prescribing.

Methods

This PAR study to improve antibiotic prescribing quality in OOH care uses a mixed methods approach. In a first exploratory phase, we will develop a partnership with a GPC and map the existing barriers and opportunities. In a second phase, we will focus on facilitating change and implementing interventions through PDSA (Plan-Do-Study-Act) cycles. In a third phase, antibiotic prescribing quality outside and antibiotic use during office hours will be evaluated. Equally important are the process evaluation and theory building on improving antibiotic prescribing.

Ethics

The study protocol was approved by the Ethics Committee of the Antwerp University Hospital/University of Antwerp. PAR unfolds in response to the needs and issues of the stakeholders, therefore new ethics approval will be obtained at each new stage of the research.

Dissemination

Interventions to improve antibiotic prescribing are needed now more than ever and outcomes will be highly relevant for GPCs, GPs in daily practice, national policymakers and the international scientific community.

Trial registration number

NCT03082521; Pre-results.

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Health-related quality of life variations by sociodemographic factors and chronic conditions in three metropolitan cities of South Asia: the CARRS study

Objectives

Health-related quality of life (HRQOL) is a key indicator of health. However, HRQOL data from representative populations in South Asia are lacking. This study aims to describe HRQOL overall, by age, gender and socioeconomic status, and examine the associations between selected chronic conditions and HRQOL in adults from three urban cities in South Asia.

Methods

We used data from 16 287 adults aged ≥20 years from the baseline survey of the Centre for Cardiometabolic Risk Reduction in South Asia cohort (2010–2011). HRQOL was measured using the European Quality of Life Five Dimension—Visual Analogue Scale (EQ5D-VAS), which measures health status on a scale of 0 (worst health status) to 100 (best possible health status).

Results

16 284 participants completed the EQ5D-VAS. Mean age was 42.4 (±13.3) years and 52.4% were women. 14% of the respondents reported problems in mobility and pain/discomfort domains. Mean VAS score was 74 (95% CI 73.7 to 74.2). Significantly lower health status was found in elderly (64.1), women (71.6), unemployed (68.4), less educated (71.2) and low-income group (73.4). Individuals with chronic conditions reported worse health status than those without (67.4 vs 76.2): prevalence ratio, 1.8 (95% CI 1.61 to 2.04).

Conclusions

Our data demonstrate significantly lower HRQOL in key demographic groups and those with chronic conditions, which is consistent with previous studies. These data provide insights on inequalities in population health status, and potentially reveal unmet needs in the community to guide health policies.

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Early sexual experiences of teenage heterosexual males in Australia: a cross-sectional survey

Objective

There are limited data on the patterns of early sexual behaviours among Australian teenage heterosexual boys. This study describes the nature and onset of early sexual experiences in this population through a cross-sectional survey.

Design

A cross-sectional survey between 2014 and 2015

Setting

Major sexual health clinics and community sources across Australia

Participants

Heterosexual men aged 17–19 years

Results

There were 191 men in the study with a median age of 19.1 years. Median age at first oral sex was 16.4 years (IQR: 15.5–17.7) and 16.9 years (IQR: 16.0–18.0) for first vaginal sex. Most men had engaged in oral sex (89.5%) and vaginal sex (91.6%) in the previous 12 months with 32.6% reporting condom use at last vaginal sex. Of the total lifetime female partners for vaginal sex reported by men as a group (n=1187): 54.3% (n=645) were the same age as the man, 28.3% (n=336) were a year or more younger and 17.4% (n=206) were a year or more older. Prior anal sex with females was reported by 22% with 47% reporting condom use at last anal sex. Median age at first anal sex was 18.2 years (IQR: 17.3–18.8). Anal sex with a female was associated with having five or more lifetime female sexual partners for oral and vaginal sex.

Conclusions

These data provide insights into the trajectory of sexual behaviours experienced by teenage heterosexual boys following sexual debut, findings which can inform programme promoting sexual health among teenage boys.

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Probiotics administered intravaginally as a complementary therapy combined with antibiotics for the treatment of bacterial vaginosis: a systematic review protocol

Introduction

Bacterial vaginosis (BV) is a highly prevalent vaginal polymicrobial disorder commonly encountered in women of childbearing age. Therapy with only recommended antibiotics results in low cure rates and unacceptably high recurrence rates. The use of probiotics as a complementary approach for use with antibiotics for the treatment of BV remains unclear. This review aims to assess the efficacy of lactobacilli administered intravaginally in conjunction with antibiotics for the treatment of BV.

Methods and analysis

The Cochrane Central Register of Controlled Trials in The Cochrane Library, Cochrane Library of Systematic Reviews, Medline/PubMed and Embase will be used to search for articles from database inception to November 2016. Randomised controlled clinical trials using lactobacilli administered intravaginally in conjunction with antibiotics to treat BV will be included. Primary outcome will be the BV cure rate. The recurrence rate will be examined as secondary outcome. Two reviewers will independently select trials and extract data from the original publications. The risk of bias will be assessed according to the Cochrane Risk of Bias tool. We will perform data synthesis using the Review Manager (RevMan) software V.5.2.3. To assess heterogeneity, we will compute the I² statistic.

Ethics and dissemination

This study will be a review of published data and it is not necessary to obtain ethical approval. Findings of this systematic review will be published in a peer-reviewed journal.

Trial registration number

International Prospective Register of Systematic Reviews 2014: CRD42014015079.

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Predictability of Recurrence using Immunohistochemistry to delineate Surgical Margins in mucosal Head and Neck Squamous Cell Carcinoma (PRISM-HNSCC): study protocol for a prospective, observational and bilateral study in Australia and India

Objectives

Treatment failure and poor 5-year survival in mucosal head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to advanced stage of presentation and high rates of recurrence. Incomplete surgical removal of the tumour, attributed to lack of reliable methods to delineate the surgical margins, is a major cause of disease recurrence. The predictability of recurrence using immunohistochemistry (IHC) to delineate surgical margins (PRISM) in mucosal HNSCC study aims to redefine margin status by identifying the true extent of the tumour at the molecular level by performing IHC with molecular markers, eukaryotic initiation factor, eIF4Eand tumour suppressor gene, p53, on the surgical margins and test the use of Lugol's iodine and fluorescence visualisation prior to the wide local excision. This article describes the study protocol at its pre - results stage.

Methods and analysis

PRISM-HNSCC is a bilateral observational research being conducted in Darwin, Australia and Vellore, India. Individuals diagnosed with HNSCC will undergo the routine wide local excision of the tumour followed by histopathological assessment. Tumours with clear surgical margins that satisfy the exclusion criteria will be selected for further staining of the margins with eIF4E and p53 antibodies. Results of IHC staining will be correlated with recurrences in an attempt to predict the risk of disease recurrence. Patients in Darwin will undergo intraoperative staining of the lesion with Lugol's iodine and fluorescence visualisation to delineate the excision margins while patients in Vellore will not undertake these tests. The outcomes will be analysed.

Ethics and dissemination

The PRISM-HNSCC study was approved by the institutional ethics committees in Darwin (Human Research Ethics Committee 13-2036) and Vellore (Institutional Review Board Min. no. 8967). Outcomes will be disseminated through publications in academic journals and presentations at educational meetings and conferences. It will be presented as dissertation at the Charles Darwin University. We will communicate the study results to both participating sites. Participating sites will communicate results with patients who have indicated an interest in knowing the results.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12616000715471).

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Maternal body mass index and the prevalence of spontaneous and elective preterm deliveries in an Irish obstetric population: a retrospective cohort study

Objective

To estimate the association between maternal body mass index (BMI) and risk of spontaneous preterm delivery (sPTD) and elective preterm delivery (ePTD) in singleton and multiple pregnancies.

Design

Retrospective cohort study.

Setting

Electronic records of all deliveries from 2009 through 2013 in a tertiary university hospital were abstracted for demographic and obstetrical information.

Participants

A total of 38 528 deliveries were included. Participants with missing data were excluded from the study. BMI was calculated from the measurement of height and weight at the first prenatal visit and categorised. Sonographic confirmation of gestational age was standard.

Outcome measures

Primary outcomes, sPTD and ePTD in singleton and multiple pregnancies, were evaluated by multinomial logistic regression analyses, stratified by parity, controlling for confounding variables.

Results

Overall rate of PTD was 5.9%, from which 2.7% were sPTD and 3.2% ePTD. The rate of PTD was 50.4% in multiple pregnancies and 5.0% in singleton pregnancies. The risk of sPTD was increased in obese nulliparas (adjusted OR (aOR) 2.8, 95% CI 1.7 to 4.4) and underweight multiparas (aOR 2.2, 95% CI 1.3 to 3.8). The risk of ePTD was increased in underweight nulliparas (aOR 1.8; 95% CI 1.04 to 3.4) and severely obese multiparas (aOR 1.4, 95% CI 1.02 to 3.8).

Severe obesity increased the risk of both sPTD (aOR 1.4; 95% CI 1.01 to 2.1) and ePTD (aOR 1.4; 95% CI 1.1 to 1.8) in singleton pregnancies. Obesity did not influence the rate of either sPTD or ePTD in multiple pregnancies.

Conclusion

Maternal obesity is an independent risk factor for PTD in singleton pregnancies but not in multiple pregnancies. Obesity and nulliparity increase the risk of sPTD, whereas obesity and multiparity increase the risk of ePTD.

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Cervical and breast cancer screening participation and utilisation of maternal health services: a cross-sectional study among immigrant women in Southern Italy

Objectives

Women make up approximately half of the world's one billion migrants. Immigrant women tend to be one of the most vulnerable population groups with respect to healthcare. Cancer screening (CS) and maternal and reproductive health have been included among the 10 main issues pertinent to women's health. The aim of this study is to explore breast and cervical CS participation and to acquire information regarding access to healthcare services during pregnancy, childbirth and the postpartum period among age eligible immigrant women in Southern Italy.

Methods

A structured questionnaire was used to collect data from each participant. Women aged 25–64 years who had not had a hysterectomy and women aged 50–69 years without history of breast cancer were considered eligible for the evaluation of cervical and breast CS participation, respectively. Moreover, women who had delivered at least once in Italy were enrolled to describe antenatal and postpartum care services use. All women were recruited through the third sector and non-profit organisations (NPOs).

Results

Rate of cervical CS among the 419 eligible women was low (39.1%), and about one-third had had a Pap test for screening purposes within a 3-year period from interview (32.8%). Regarding breast CS practices, of the 125 eligible women 45.6% had had a mammography for control purposes and less than a quarter (26, 20.8%) had their mammography within the recommended time interval of 2 years. About 80% of the respondents did not report difficulties of access and use of antenatal and postpartum services.

Conclusion

This study provides currently unavailable information about adherence to CS and maternal and child health that could encourage future research to develop and test culturally appropriate, women-centred strategies for promoting timely and regular CS among immigrant women in Italy.

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Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus

Recent genomic data have revealed multiple interactions between Neanderthals and modern humans1, but there is currently little genetic evidence regarding Neanderthal behaviour, diet, or disease. Here we describe the shotgun-sequencing of ancient DNA from five specimens of Neanderthal calcified dental plaque (calculus) and the characterization of regional differences in Neanderthal ecology. At Spy cave, Belgium, Neanderthal diet was heavily meat based and included woolly rhinoceros and wild sheep (mouflon), characteristic of a steppe environment. In contrast, no meat was detected in the diet of Neanderthals from El Sidrón cave, Spain, and dietary components of mushrooms, pine nuts, and moss reflected forest gathering2, 3. Differences in diet were also linked to an overall shift in the oral bacterial community (microbiota) and suggested that meat consumption contributed to substantial variation within Neanderthal microbiota. Evidence for self-medication was detected in an El Sidrón Neanderthal with a dental abscess4 and a chronic gastrointestinal pathogen (Enterocytozoon bieneusi). Metagenomic data from this individual also contained a nearly complete genome of the archaeal commensal Methanobrevibacter oralis (10.2× depth of coverage)—the oldest draft microbial genome generated to date, at around 48,000 years old. DNA preserved within dental calculus represents a notable source of information about the behaviour and health of ancient hominin specimens, as well as a unique system that is useful for the study of long-term microbial evolution.

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The interdependence of personality and satisfaction in couples

Personality has been found to play an important role in predicting satisfaction in couples. This review presents dyadic research on the association between Big Five traits and both life and relationship satisfaction in couples focusing on self-reported personality, partner-perceived personality (how the partner rates one's own personality), and personality similarity. Furthermore, special attention is given to possible gender effects. The findings indicate the importance of self-reported as well as partner-perceived reported personality for the satisfaction of both partners. Specifically, the majority of studies found intrapersonal and interpersonal effects for neuroticism, agreeableness, and conscientiousness on life or relationship satisfaction. For the partner-perceived personality, intrapersonal and interpersonal effects were present for all Big Five traits. Partners' similarity in personality traits seems not to be related with their satisfaction when controlling for partners' personality.

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The association of mothers' and fathers' insomnia symptoms with school-aged children's sleep assessed by parent report and in-home sleep-electroencephalography

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High-Speed Atomic Force Microscopy Visualization of the Dynamics of the Multienzyme Fatty Acid Synthase

Multienzymes, such as the protein metazoan fatty acid synthase (FAS), are giant and highly dynamic molecular machines for critical biosynthetic processes. The molecular architecture of FAS was elucidated by static high-resolution crystallographic analysis, while electron microscopy revealed large-scale conformational variability in FAS with some correlation to functional states in catalysis. However, little is known about time scales of conformational dynamics, the trajectory of motions in individual FAS molecules and the extent of coupling between catalysis and structural changes. Here, we present an experimental single-molecule approach to film immobilized or selectively tethered FAS in solution at different viewing angles and high spatio-temporal resolution using high-speed atomic force microscopy (HS-AFM). Mobility of individual regions of the multienzyme is recognized in video sequences and correlation of shape features implies a convergence of temporal resolution and velocity of FAS dynamics. Conformational variety can be identified and grouped by reference-free 2D class averaging, enabling the tracking of conformational transitions in movies. The approach presented here is suited for comprehensive studies of the dynamics of FAS and other multienzymes in aqueous solution at the single-molecule level.

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Morphometric and histologic characterization of alveolar bone from hypertensive patients

Abstract

Background

Hypertension is considered a risk factor in implant dentistry but the underlying reasons remain unclear. It may be that hypertension has a negative impact on the local bone quality.

Purpose

Here we evaluated the structural and histological parameters of bone collected from hypertensive patients treated by antagonists of the renin-angiotensin system, and of bone collected from normotensive patients.

Material and methods

A total of 30 patients were referred for rehabilitation with dental implants to be placed in the posterior mandible. The first group were hypertensive patients treated with RAS antagonists. The second group were normotensive patients not taking medication. Bone biopsies collected during implant installation were subjected to analysis. Micro CT revealed the structural parameters. Histological analyses together with immunohistochemical staining of osteogenic markers were performed.

Results

The structural parameters of bone volume, trabecular thickness, trabecular number, separation of the trabecular, and total porosity were similar between the 2 groups (P > .05). The histological appearance of bone derived from hypertensive patients was normal. The staining pattern of Runx-2, osteopontin, and osteocalcin were comparable in both groups.

Conclusions

These observations suggest that hypertensive patients treated with renin-angiotensin system antagonists have regular alveolar bone with respect to bone structure and histological parameters.

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A prospective, split-mouth study comparing tilted implants with angulated connection versus conventional implants with angulated abutment

Abstract

Background

An angulation of the implant connection could overcome the problems related to angulated abutments.

Purpose

This study compares conventional implants with angulated abutment to tilted implants with an angulated connection.

Materials and Methods

Twenty patients were treated in the edentulous mandible. In the posterior jaw locations, one conventional tilted implant with angulated abutment and one angulated implant without abutment were placed. In the anterior jaw, two conventional implants were placed, one with and one without abutment. Implants were immediately loaded and 3 months later, the final bridge (PFM or monolithic zirconia) was placed.

Results

After a follow-up of 48 months, 17 patients were available for clinical examination. The mean overall marginal bone loss (MBL) was 1.26 mm. No significant differences in implant survival, MBL, periodontal indices, patients' satisfaction, or complications was found between implants restored on abutment or implant level, between the posteriorly located angulated implant nor angulated abutment, and between both anterior implants with or without abutment. The posterior implants demonstrated less MBL compared to the anterior implants (P < .001). There was no significant difference in MBL between the implants restored with zirconia or PFM bridges (P = .294). Overall mean pocket depth was 2.83 mm. More plaque was found in the PFM group compared to the full-zirconia group, at the bridge (P = .042) and the implants (P = .029). There was no difference between both materials in pocket depth (P = .635) or bleeding (P = .821). One zirconia bridge fractured, two angulated abutment were replaced and four loose bridge screws connected to the angulated abutments had to be tightened. Patients were overall satisfied (4.74/5).

Conclusion

An implant with angulated connection may results in a stronger connection but does not affect the marginal bone loss. No difference in MBL was seen between implants restored on abutment or implant level. Zirconia seems to reduce the amount of plaque.

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A prospective randomized controlled trial of the two-window technique without membrane versus the solo-window technique with membrane over the osteotomy window for maxillary sinus augmentation

Abstract

Background

Maturation of the grafted volume after lateral sinus elevation is crucial for the long-term survival of dental implants.

Purpose

To compare endo-sinus histomorphometric bone formation between the solo- and two-window maxillary sinus augmentation techniques with or without membrane coverage for the rehabilitation of multiple missing posterior teeth.

Materials and Methods

Patients with severely atrophic posterior maxillae were randomized to receive lateral sinus floor elevation via the solo-window technique with membrane coverage (Control Group) or the two-window technique without coverage (Test Group). Six months after surgery, bone core specimens harvested from the lateral aspect were histomorphometrically analyzed.

Results

Ten patients in each group underwent 21 maxillary sinus augmentations. Histomorphometric analysis revealed mean newly formed bone values of 26.08 ± 16.23% and 27.14 ± 18.11%, mean connective tissue values of 59.34 ± 12.42% and 50.03 ± 17.13%, and mean residual graft material values of 14.6 ± 14.56% and 22.78 ± 10.83% in the Test and Control Groups, respectively, with no significant differences.

Conclusions

The two-window technique obtained comparative maturation of the grafted volume even without membrane coverage, and is a viable alternative for the rehabilitation of severely atrophic posterior maxillae with multiple missing posterior teeth.

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In Vitro Antioxidant, Antihemolytic, and Anticancer Activity of the Carotenoids from Halophilic Archaea

Abstract

Halophilic archaea represent a promising natural source of carotenoids. However, little information is available about the biological effects of carotenoids from halophilic archaea. In this study, the carotenoids produced by seven halophilic archaeal strains Halogeometricum rufum, Halogeometricum limi, Haladaptatus litoreus, Haloplanus vescus, Halopelagius inordinatus, Halogranum rubrum, and Haloferax volcanii were identified by ultraviolet/visible spectroscopy, thin-layer chromatography, and high-performance liquid chromatography-tandem mass spectrometry. The C₅₀ carotenoids bacterioruberin and its derivatives monoanhydrobacterioruberin and bisanhydrobacterioruberin were found to be the predominant carotenoids. The antioxidant capacities of the carotenoids from these strains were significantly higher than β-carotene as determined by 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. The antihemolytic activities of these carotenoid extracts against H₂O₂-induced hemolysis in mouse erythrocytes were 3.9–6.3 times higher than β-carotene. A dose-dependent in vitro antiproliferative activity against HepG2 cells was observed for the extract from Hgm. limi, while that from Hpn. vescus exhibited a relatively high activity in a dose-independent manner. These results suggested that halophilic archaea could be considered as an alternative source of natural carotenoids with high antioxidant, antihemolytic, and anticancer activity.

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The Pathways fertility preservation decision aid website for women with cancer: development and field testing

Abstract

Purpose

To improve survivors' awareness and knowledge of fertility preservation counseling and treatment options, this study engaged survivors and providers to design, develop, and field-test Pathways: a fertility preservation patient decision aid website for young women with cancer©.

Methods

Using an adapted user-centered design process, our stakeholder advisory group and research team designed and optimized the Pathways patient decision aid website through four iterative cycles of review and revision with clinicians (n = 21) and survivors (n = 14). Field-testing (n = 20 survivors) assessed post-decision aid scores on the Fertility Preservation Knowledge Scale, feasibility of assessing women's decision-making values while using the website, and website usability/acceptability ratings.

Results

Iterative stakeholder engagement optimized the Pathways decision aid website to meet survivors' and providers' needs, including providing patient-friendly information and novel features such as interactive value clarification exercises, testimonials that model shared decision making, financial/referral resources, and a printable personal summary. Survivors scored an average of 8.2 out of 13 (SD 1.6) on the Fertility Preservation Knowledge Scale. They rated genetic screening and having a biological child as strong factors in their decision-making, and 71% indicated a preference for egg freezing. Most women (> 85%) rated Pathways favorably, and all women (100%) said they would recommend it to other women.

Conclusions

The Pathways decision aid is a usable and acceptable tool to help women learn about fertility preservation.

Implications for Cancer Survivors

The Pathways decision aid may help women make well-informed values-based decisions and prevent future infertility-related distress.

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Dysregulation of Sleep Behavioral States in Narcolepsy.

Dysregulation of Sleep Behavioral States in Narcolepsy.

Sleep. 2017 Oct 05;:

Authors: Schoch SF, Werth E, Poryazova R, Scammell TE, Baumann CR, Imbach LL

Abstract
Study Objectives: Patients with narcolepsy suffer from poor maintenance of wakefulness and fragmented night sleep, but the underlying mechanism of sleep boundary dysregulation remains little understood. The goal of this study was to quantify abnormal sleep-wake regulation in narcolepsy patients.
Methods: Using a model-based approach (state space analysis), we analyzed overnight EEG recordings in ten patients with narcolepsy type 1 and age- and gender-matched healthy control subjects. We analyzed consolidated sleep states using cluster analysis in state space and transitional sleep periods as trajectories between stable clusters.
Results: Patients with narcolepsy showed a dislocation of REM sleep in state space and overlap of REM and WAKE behavioral states. Narcolepsy patients had more trajectories between the REM and the WAKE clusters, and also between the NREM and WAKE clusters. Point density analysis showed more transitional periods between WAKE and REM in narcolepsy, less consolidated NREM sleep, and higher velocities between WAKE and NREM in patients. Conventional sleep analysis revealed increased NREM1 and decreased NREM2 sleep and reduced REM latency in narcolepsy patients.
Conclusions: This study provides further evidence for narcolepsy as a disorder of state boundaries including, but not limited to REM sleep and wakefulness. In particular, the increase in transitional periods between REM and WAKE, but also between NREM and WAKE indicates abnormal state dynamics in narcolepsy. This pattern may be a consequence of disrupted sleep/wake stabilizing mechanisms due to loss of hypocretin/orexin neurons in the hypothalamus.

PMID: 29029348 [PubMed - as supplied by publisher]

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Childhood Health and Educational Outcomes Associated with Maternal Sleep Apnea: A Population Record-Linkage Study.

Childhood Health and Educational Outcomes Associated with Maternal Sleep Apnea: A Population Record-Linkage Study.

Sleep. 2017 Oct 05;:

Authors: Bin YS, Cistulli PA, Roberts CL, Ford JB

Abstract
Objectives: Sleep apnea in pregnancy is known to adversely affect birth outcomes. Whether in utero exposure to maternal sleep apnea is associated with long-term childhood consequences is unclear.
Methods: Population-based longitudinal study of singleton infants born during 2002 to 2012 was conducted using linked birth, hospital, death, developmental, and educational records from New South Wales, Australia. Maternal sleep apnea during pregnancy was identified from hospital records. Outcomes were mortality and hospitalisations up to age 6, developmental vulnerability in the 1st year of school (aged 5-6), and performance on standardised tests in the 3rd year of school (aged 7-9). Cox proportional hazards and modified Poisson regression models were used to calculate hazard and risk ratios for outcomes in children exposed to maternal apnea compared to those not exposed.
Results: 209 of 626,188 singleton infants were exposed to maternal sleep apnea. Maternal apnea was not significantly associated with mortality (Fisher's exact p=0.48), developmental vulnerability (adjusted RR 1.29; 95% CI 0.75-2.21), special needs status (1.58; 0.61-4.07), or low numeracy test scores (1.03; 0.63-1.67) but was associated with low reading test scores (1.55; 1.08-2.23). Maternal apnea significantly increased hospitalisations in the 1st year of life (adjusted HR 1.81; 95% CI 1.40-2.34) and between the 1st and 6th birthdays (1.41; 1.14-1.75). This is partly due to admissions for suspected paediatric sleep apnea.
Conclusions: Maternal sleep apnea during pregnancy is associated with poorer childhood health. Its impact on developmental and cognitive outcomes warrants further investigation.

PMID: 29029347 [PubMed - as supplied by publisher]

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Circadian Phase and Phase Angle Disorders in Primary Insomnia.

Circadian Phase and Phase Angle Disorders in Primary Insomnia.

Sleep. 2017 Oct 03;:

Authors: Flynn-Evans EE, Shekleton JA, Miller B, Epstein LJ, Kirsch D, Brogna LA, Burke LM, Bremer E, Murray JM, Gehrman P, Rajaratnam SMW, Lockley SW

Abstract
Objectives: We aimed to identify the prevalence of circadian phase and phase angle abnormalities in patients with insomnia.
Methods: We conducted a cross-sectional, multicenter study at three sleep laboratories in the United States and Australia. Patients with insomnia and healthy control participants completed a sleep log for seven days. Circadian phase was assessed from salivary Dim Light Melatonin Onset (DLMO) time during a 12-hour laboratory visit.
Results: Seventy-nine patients meeting the Research Diagnostic Criteria for Primary, Psychophysiological, Paradoxical, and/or Idiopathic Childhood Insomnia (46F, 35.5 ± 12.3 years (M SD)) and 21 controls (14F, 34.4 11.8 years). As compared to controls, patients with insomnia tried to initiate sleep on average at the same clock time (24:17 ± 1:17 h versus 24:13 ± 1:30 h, respectively; p=0.84), but had a later average DLMO times (20:56 ± 1:55 h, 18:17 - 01:21 versus 22:02 ± 2:02 h, 17:11 - 04:52, respectively; p=0.04). Consequently, patients with insomnia slept at an earlier circadian phase than controls (phase angle, bedtime-DLMO 2:13 h (± 1:43) versus 3:10 h (± 1:08), respectively; p=0.008), of whom 10% tried to sleep at or before DLMO (compared to 0 controls), and 22% tried to sleep before or within 1 hour after DLMO (compared to 6% of controls).
Conclusions: A substantial proportion (10-22%) of patients with insomnia initiate sleep at too early a circadian phase, implicating a circadian etiology for their insomnia. Outpatient circadian phase assessments should be considered to improve differential diagnoses in insomnia and to inform the development of appropriately timed circadian-based treatments.

PMID: 29029340 [PubMed - as supplied by publisher]

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Eliminating the Controlled Napping Policy at CSX Is a Blow to Public Safety.

Eliminating the Controlled Napping Policy at CSX Is a Blow to Public Safety.

Sleep. 2017 Sep 19;:

Authors: Hursh SR, Drummond SPA

PMID: 29029318 [PubMed - as supplied by publisher]

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Subjective-Objective Sleep Discrepancy is Associated with Alterations in Regional Glucose Metabolism in Patients with Insomnia and Good Sleeper Controls.

Subjective-Objective Sleep Discrepancy is Associated with Alterations in Regional Glucose Metabolism in Patients with Insomnia and Good Sleeper Controls.

Sleep. 2017 Oct 03;:

Authors: Kay DB, Karim HT, Soehner AM, Hasler BP, James JA, Germain A, Hall MH, Franzen PL, Price JC, Nofzinger EA, Buysse DJ

Abstract
Objectives: Sleep discrepancies are common in primary insomnia (PI), and include reports of longer sleep onset latency (SOL) than measured by polysomnography (PSG), or "negative SOL discrepancy." We hypothesized that negative SOL discrepancy in PI would be associated with higher relative glucose metabolism during non-rapid eye movement (NREM) sleep in brain networks involved in conscious awareness, including the salience, left executive control, and default mode networks.
Methods: PI (n=32) and good sleeper controls (GS; n=30) completed [ 18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans during NREM sleep and relative regional cerebral metabolic rate for glucose (rCMRglc) was measured. Sleep discrepancy was calculated by subtracting PSG-measured SOL on the PET night from corresponding self-report values the following morning. We tested for interactions between group (PI vs. GS) and SOL discrepancy for rCMRglc during NREM sleep using both a region of interest mask and exploratory whole-brain analyses.
Results: Significant group by SOL discrepancy interactions for rCMRglc were observed in several brain regions (pcorrected<0.05 for all clusters). In the PI group, more negative SOL discrepancy (self-reported>PSG-measured SOL) was associated with significantly higher relative rCMRglc in the right anterior insula and middle/posterior cingulate during NREM sleep. In GS, more positive SOL discrepancy (self-reported<PSG-measured SOL) was associated with significantly higher relative rCMRglc in the right anterior insula, left anterior cingulate cortex, and middle/posterior cingulate cortex.
Conclusions: Although preliminary, these findings suggest regions of the brain previously shown to be involved in conscious awareness and the perception of PSG-defined states may also be involved in the phenomena of SOL discrepancy.

PMID: 29029313 [PubMed - as supplied by publisher]

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Limited efficacy of caffeine and recovery costs during and following 5 days of chronic sleep restriction: Caffeine and Sleep Restriction.

Limited efficacy of caffeine and recovery costs during and following 5 days of chronic sleep restriction: Caffeine and Sleep Restriction.

Sleep. 2017 Oct 05;:

Authors: Doty TJ, So CJ, Bergman EM, Trach SK, Ratcliffe RH, Yarnell AM, Capaldi VF, Moon JE, Balkin TJ, Quartana PJ

Abstract
Objectives: To investigate the effects of caffeine on psychomotor vigilance and sleepiness during sleep restriction and following subsequent recovery sleep.
Methods: Participants were N=48 healthy good sleepers. All participants underwent 5 nights of sleep satiation [time-in-bed (TIB): 10 hrs], followed by 5 nights of sleep restriction (TIB: 5 hrs), and 3 nights of recovery sleep (TIB: 8 hrs) in a sleep laboratory. Caffeine (200 mg) or placebo was administered in the form of chewing gum at 0800 and 1200 hrs each day during the sleep restriction phase. Participants completed hourly 10-min psychomotor vigilance tests (PVTs) and a modified Maintenance of Wakefulness Test approximately every 4 hours during the sleep restriction and recovery phases.
Results: Caffeine maintained objective alertness compared to placebo across the first three days of sleep restriction, but this effect was no longer evident by the fourth day. A similar pattern of results was found for MWT sleep latencies, such that those in the caffeine group (compared to placebo) did not show maintenance of wakefulness relative to baseline after the second night of restriction. Compared to placebo, participants in the caffeine condition displayed slower return to baseline in alertness and wakefulness across the recovery sleep period. Lastly, the caffeine group showed greater N3 sleep duration during recovery.
Conclusions: Caffeine appears to have limited efficacy for maintaining alertness and wakefulness across 5 days of sleep restriction. Perhaps more importantly, there may be recovery costs associated with caffeine use following conditions of prolonged sleep loss.

PMID: 29029309 [PubMed - as supplied by publisher]

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Large-Scale Automated Sleep Staging.

Large-Scale Automated Sleep Staging.

Sleep. 2017 Sep 26;:

Authors: Sun H, Jia J, Goparaju B, Huang GB, Sourina O, Bianchi MT, Westover MB

Abstract
Study Objectives: Automated sleep staging has been previously limited by a combination of clinical and physiological heterogeneity. Both factors are in principle addressable with large data sets that enable robust calibration. However, the impact of sample size remains uncertain. The objectives are to investigate the extent to which machine learning methods can approximate the performance of human scorers when supplied with sufficient training cases and to investigate how staging performance depends on the number of training patients, contextual information, model complexity, and imbalance between sleep stage proportions.
Methods: A total of 102 features were extracted from six electroencephalography (EEG) channels in routine polysomnography. Two thousand nights were partitioned into equal (n = 1000) training and testing sets for validation. We used epoch-by-epoch Cohen's kappa statistics to measure the agreement between classifier output and human scorer according to American Academy of Sleep Medicine scoring criteria.
Results: Epoch-by-epoch Cohen's kappa improved with increasing training EEG recordings until saturation occurred (n = ~300). The kappa value was further improved by accounting for contextual (temporal) information, increasing model complexity, and adjusting the model training procedure to account for the imbalance of stage proportions. The final kappa on the testing set was 0.68. Testing on more EEG recordings leads to kappa estimates with lower variance.
Conclusion: Training with a large data set enables automated sleep staging that compares favorably with human scorers. Because testing was performed on a large and heterogeneous data set, the performance estimate has low variance and is likely to generalize broadly.

PMID: 29029305 [PubMed - as supplied by publisher]

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Acute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs Contextual Memory in Adult Rats.

Acute Kynurenine Challenge Disrupts Sleep-Wake Architecture and Impairs Contextual Memory in Adult Rats.

Sleep. 2017 Sep 28;:

Authors: Pocivavsek A, Baratta AM, Mong JA, Viechweg SS

Abstract
Study Objectives: Tryptophan metabolism via the kynurenine pathway may represent a key molecular link between sleep loss and cognitive dysfunction. Modest increases in the kynurenine pathway metabolite kynurenic acid (KYNA), which acts as an antagonist at N-methyl-d-aspartate and α7 nicotinic acetylcholine receptors in the brain, result in cognitive impairments. As glutamatergic and cholinergic neurotransmissions are critically involved in modulation of sleep, our current experiments tested the hypothesis that elevated KYNA adversely impacts sleep quality.
Methods: Adult male Wistar rats were treated with vehicle (saline) and kynurenine (25, 50, 100, and 250 mg/kg), the direct bioprecursor of KYNA, intraperitoneally at zeitgeber time (ZT) 0 to rapidly increase brain KYNA. Levels of KYNA in the brainstem, cortex, and hippocampus were determined at ZT 0, ZT 2, and ZT 4, respectively. Analyses of vigilance state-related parameters categorized as wake, rapid eye movement (REM), and non-REM (NREM) as well as spectra power analysis during NREM and REM were assessed during the light phase. Separate animals were tested in the passive avoidance paradigm, testing contextual memory.
Results: When KYNA levels were elevated in the brain, total REM duration was reduced and total wake duration was increased. REM and wake architecture, assessed as number of vigilance state bouts and average duration of each bout, and theta power during REM were significantly impacted. Kynurenine challenge impaired performance in the hippocampal-dependent contextual memory task.
Conclusions: Our results introduce kynurenine pathway metabolism and formation of KYNA as a novel molecular target contributing to sleep disruptions and cognitive impairments.

PMID: 29029302 [PubMed - as supplied by publisher]

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Nutrition Influences Caffeine-Mediated Sleep Loss in Drosophila.

Nutrition Influences Caffeine-Mediated Sleep Loss in Drosophila.

Sleep. 2017 Oct 03;:

Authors: Keebaugh ES, Park JH, Su C, Yamada R, Ja WW

Abstract
Study objectives: Plant-derived caffeine is regarded as a defensive compound produced to prevent herbivory. Caffeine is generally repellent to insects and often used to study the neurological basis for aversive responses in the model insect, Drosophila melanogaster. Caffeine is also studied for its stimulatory properties where sleep or drowsiness is suppressed across a range of species. Since limiting access to food also inhibits fly sleep-an effect known as starvation-induced sleep suppression-we tested whether aversion to caffeinated food results in reduced nutrient intake and assessed how this might influence fly studies on the stimulatory effects of caffeine.
Methods: We measured sleep and total consumption during the first 24 hours of exposure to caffeinated diets containing a range of sucrose concentrations to determine the relative influence of caffeine and nutrient ingestion on sleep. Experiments were replicated using three fly strains.
Results: Caffeine reduced total consumption and nighttime sleep, but only at intermediate sucrose concentrations. Although sleep can be modeled by an exponential dose response to nutrient intake, caffeine-mediated sleep loss cannot be explained by absolute caffeine or sucrose ingestion alone. Instead, reduced sleep strongly correlates with changes in total consumption due to caffeine. Other bitter compounds phenocopy the effect of caffeine on sleep and food intake.
Conclusions: Our results suggest that a major effect of dietary caffeine is on fly feeding behavior. Changes in feeding behavior may drive caffeine-mediated sleep loss. Future studies using psychoactive compounds should consider the potential impact of nutrition when investigating effects on sleep.

PMID: 29029291 [PubMed - as supplied by publisher]

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NMDA Receptor-mediated Ca2+ Influx in the Absence of Mg2+ Block Disrupts Rest:activity Rhythms in Drosophila.

NMDA Receptor-mediated Ca2+ Influx in the Absence of Mg2+ Block Disrupts Rest:activity Rhythms in Drosophila.

Sleep. 2017 Oct 03;:

Authors: Song Q, Feng G, Zhang J, Xia X, Ji M, Lv L, Ping Y

Abstract
Introduction: The correlated activation of pre- and postsynaptic neurons is essential for the NMDA receptor-mediated Ca2+ influx by removing Mg2+ from block site and NMDA receptors have been implicated in phase resetting of circadian clocks. So we assessed rest:activity rhythms in Mg2+ block defective animals.
Methods: Using Drosophila locomotor monitoring system, we checked circadian rest:activity rhythms of different mutants under constant darkness (DD) and light:dark (LD) conditions. We recorded NMDA receptor-mediated currents or Ca2+ increase in neurons using patch-clamp and Ca2+ imaging techniques.
Results: We found that Mg2+ block defective mutant flies exhibited completely arrhythmic under DD. To further understand the role of Mg2+ block in daily circadian rest:activity, we observed the mutant files under LD cycles, and we found severely reduced morning anticipation and advanced evening peak compared to control flies. We also used tissue-specific expression of Mg2+ block defective NMDA receptors and demonstrated pigment-dispersing factor receptor (PDFR) expressing circadian neurons were implicated in mediating the circadian rest:activity deficits. Endogenous functional NMDA receptors are expressed in most Drosophila neurons, including in a subgroup of dorsal neurons (DN1s). Subsequently, we determined that the uncorrelated extra Ca2+ influx may act in part through Ca2+/Calmodulin (CaM)-stimulated PDE1c pathway leading to morning behavior phenotypes.
Conclusions: These results demonstrate that Mg2+ block of NMDA receptors at resting potential is essential for the daily circadian rest:activity and we propose that Mg2+ block functions to suppress CaM-stimulated PDE1c activation at resting potential, thus regulating Ca2+ and cAMP oscillations in circadian and sleep circuits.

PMID: 29029290 [PubMed - as supplied by publisher]

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The influence of CO2 on genioglossus muscle after-discharge following arousal from sleep : Hypocapnia and genioglossus muscle after-discharge.

The influence of CO2 on genioglossus muscle after-discharge following arousal from sleep : Hypocapnia and genioglossus muscle after-discharge.

Sleep. 2017 Oct 06;:

Authors: Cori JM, Rochford PD, O'Donoghue FJ, Trinder J, Jordan AS

Abstract
Objectives: Ventilatory after-discharge (sustained elevation of ventilation following stimulus removal), occurs during sleep but not when hypocapnia is present. Genioglossus after-discharge also occurs during sleep, but CO2 effects have not been assessed. The relevance is that post-arousal after-discharge may protect against upper airway collapse. This study aimed to determine whether arousal elicits genioglossus after-discharge that persists into sleep, and whether it is influenced by CO2.
Methods: 24 healthy individuals (6 female) slept with a nasal mask and ventilator. Sleep (EEG, EOG, EMG), ventilation (pneumotachograph), end-tidal CO2 (PETCO2) and intramuscular genioglossus EMG were monitored. NREM eucapnia was determined during five minutes on continuous positive airway pressure (4cmH2O). Inspiratory pressure support was increased until PETCO2 was ≥2mmHg below NREM eucapnia. Supplemental CO2 was added to reproduce normocapnia, without changing ventilator settings. Arousals were induced by auditory tones and genioglossus EMG compared during steady-state hypocapnia and normocapnia.
Results: 11 participants (4 female) provided data. Pre-arousal PETCO2 was less (p<.05) during hypocapnia (40.74±2.37) than normocapnia (43.82±2.89), with differences maintained post-arousal. After-discharge, defined as an increase in genioglossus activity above pre-arousal levels, occurred following the return to sleep. For tonic activity, after-discharge lasted four breaths irrespective of CO2 condition. For peak activity, after-discharge lasted one breath during hypocapnia and six breaths during normocapnia. However, when peak activity following the return to sleep was compared between CO2 conditions no individual breath differences were observed.
Conclusions: Post-arousal genioglossal after-discharge may protect against upper airway collapse during sleep. Steady-state CO2 levels minimally influence post-arousal genioglossus after-discharge.

PMID: 29029284 [PubMed - as supplied by publisher]

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Acupuncture Improves Peri-menopausal Insomnia: A Randomized Controlled Trial.

Acupuncture Improves Peri-menopausal Insomnia: A Randomized Controlled Trial.

Sleep. 2017 Sep 22;:

Authors: Cong F, Na Z, Zhen L, Lu-Hua Y, Chen X, Wen-Jia Y, Xin-Tong Y, Huan Y, Yun-Fei C

Abstract
Study Objective: To evaluate the short-term efficacy of acupuncture for the treatment of peri-menopausal insomnia (PMI).
Methods: Design: A randomized, participant-blind, placebo-controlled trial consisted of the acupuncture group (n=38) and placebo-acupuncture group (n=38). Setting: A tertiary teaching and general hospital. Participants: 76 peri-menopausal women with insomnia disorder based on the International Classification of Sleep Disorders, third Edition. Interventions: A 10-session of acupuncture at bilateral Shenshu (BL 23) and Ganshu (BL 18) with unilateral Qimen (LR 14) and Jingmen (GB 25) or Streitberger needles at the same acupoints was performed for over 3 weeks. Measurements: Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with over-night polysomnography (PSG) exam were completed at baseline and post-treatment.
Results: After the treatments, the decrease from baseline in PSQI score was 8.03 points in acupuncture group and 1.29 points in placebo-acupuncture group. The change from baseline in ISI score was 11.35 points in acupuncture group and 2.87 points in placebo-acupuncture group. In PSG data, acupuncture significantly improved the sleep efficiency and total sleep time, associated with less wake after sleep onset and lower percent stage 1 after the treatment. No significant differences from baseline to post-treatment were found in placebo-acupuncture group.
Conclusions: Acupuncture can contribute to a clinically relevant improvement in the short-term treatment of PMI, both subjectively and objectively.
Clinical Trial Registration: Acupuncture for peri-menopause Insomnia: a randomized controlled trial, http://ift.tt/2yost9y, ChiCTR-IPR-15007199, China.

PMID: 29029258 [PubMed - as supplied by publisher]

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Breathing disturbances without hypoxia are associated with objective sleepiness in sleep apnea.

Breathing disturbances without hypoxia are associated with objective sleepiness in sleep apnea.

Sleep. 2017 Sep 26;:

Authors: Koch H, Schneider LD, Finn LA, Leary EB, Peppard PE, Hagen E, Sorensen HBD, Jennum P, Mignot E

Abstract
Study Objectives: Determine if defining two subtypes of sleep-disordered breathing (SDB) events - with or without hypoxia - results in measures that are more strongly associated with hypertension and sleepiness.
Methods: A total of 1,022 subjects with 2,112 nocturnal polysomnograms (PSGs) from the Wisconsin Sleep Cohort were analyzed with our automated algorithm, developed to detect breathing disturbances and desaturations. Breathing events were time-locked to desaturations, resulting in 2 indices - desaturating (H-BDI) and non-desaturating (NH-BDI) events - regardless of arousals. Measures of subjective (Epworth Sleepiness Scale) and objective (2,981 multiple sleep latency tests from a subset of 865 subjects) sleepiness were analyzed, in addition to clinically relevant clinicodemographic variables. Hypertension was defined as BP ≥140/90 or antihypertensive use.
Results: H-BDI, but not NH-BDI, correlated strongly with SDB severity indices that included hypoxia (r≥0.89, p≤0.001 with 3% ODI and AHI with 4%-desaturations). A doubling of desaturation-associated events was associated with hypertension prevalence, which was significant for ODI but not H-BDI (3% ODI OR=1.06, 95% CI=1.00-1.12, p<0.05; H-BDI OR 1.04, 95% CI=0.98-1.10) and daytime sleepiness (β=0.20 ESS score, p<0.0001; β=-0.20 min in MSL on MSLT, p<0.01). Independently, non-desaturating event doubling was associated with more objective sleepiness (β=-0.52 min in MSL on MSLT, p<0.001), but had less association with subjective sleepiness (β=0.12 ESS score, p=0.10). In longitudinal analyses, baseline non-desaturating events were associated with worsening of H-BDI over a 4-year follow up, suggesting evolution in severity.
Conclusions: In SDB, non-desaturating events are independently associated with objective daytime sleepiness, beyond the effect of desaturating events.

PMID: 29029253 [PubMed - as supplied by publisher]

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Time-on-Task Effect during Sleep Deprivation in Healthy Young Adults Is Modulated by Dopamine Transporter Genotype.

Time-on-Task Effect during Sleep Deprivation in Healthy Young Adults Is Modulated by Dopamine Transporter Genotype.

Sleep. 2017 Oct 04;:

Authors: Satterfield BC, Wisor JP, Schmidt MA, Van Dongen HPA

Abstract
Study Objectives: The time-on-task (TOT) effect and total sleep deprivation (TSD) have similar effects on neurobehavioral functioning, including increased performance instability during tasks requiring sustained attention. The TOT effect is exacerbated by TSD, suggesting potentially overlapping mechanisms. We probed these mechanisms by investigating genotype-phenotype relationships on psychomotor vigilance test (PVT) performance for three a-priori selected genes previously linked to the TOT effect and/or TSD: DAT1, COMT, and TNFα.
Methods: N=82 healthy adults participated in one of three laboratory studies. A 10 min PVT was administered repeatedly during 38 h of TSD. We assessed changes in response time (RT) across each minute of the PVT as a function of time awake and genotype. Additionally, cumulative relative RT frequency distributions were constructed to examine changes in performance from the first to the second 5 min of the PVT as a function of genotype.
Results: DAT1, COMT, and TNFα were associated with differences in the build-up of the TOT effect across the 10 min PVT. DAT1 additionally modulated the interaction between TSD and the TOT effect. Subjects homozygous for the DAT1 10-repeat allele were relatively protected against TOT deficits on the PVT during TSD compared to carriers of the 9-repeat allele.
Conclusions: DAT1 is known to regulate dopamine reuptake and is highly expressed in the striatum. Our results implicate striatal dopamine in mechanisms involved in performance instability that appear to be common to TSD and the TOT effect. Furthermore, DAT1 may be a candidate biomarker of resilience to the build-up of performance impairment across TOT due to TSD.

PMID: 29029252 [PubMed - as supplied by publisher]

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Actigraphy-Derived Daily Rest-Activity Patterns and Body Mass Index in Community-Dwelling Adults.

Actigraphy-Derived Daily Rest-Activity Patterns and Body Mass Index in Community-Dwelling Adults.

Sleep. 2017 Oct 04;:

Authors: Cespedes Feliciano EM, Quante M, Weng J, Mitchell JA, James P, Marinac CR, Mariani S, Redline S, Kerr J, Godbole S, Manteiga A, Wang D, Hipp JA

Abstract
Study Objectives: To examine associations between 24-hour rest-activity patterns and body mass index (BMI) among community-dwelling U.S. adults. Rest-activity patterns provide a field method to study exposures related to circadian rhythms.
Methods: Adults (N=578) wore an actigraph on their non-dominant wrist for 7 days. Intradaily variability and interdaily stability, M10 (most active 10-hours), L5 (least active 5-hours) and relative amplitude (RA) were derived using non-parametric rhythm analysis. Mesor, acrophase, and amplitude were calculated from log-transformed count data using the parametric cosinor approach.
Results: Participants were 80% female and mean (SD) age was 52 (15) years. Participants with higher BMI had lower values for magnitude, RA, interdaily stability, total sleep time (TST), and sleep efficiency. In multivariable analyses, less robust 24-hour rest-activity patterns as represented by lower RA were consistently associated with higher BMI: comparing the bottom quintile (least robust) to the top quintile (most robust 24-hour rest-activity pattern) of RA, BMI was 3-kg/m2 higher (p=0.02). Associations were similar in magnitude to an hour less of TST (1-kg/m2 higher BMI) or a 10% decrease in sleep efficiency (2-kg/m2 higher BMI), and independent of age, sex, race, education, and the duration of rest and/or activity.
Conclusions: Lower RA, reflecting both higher night activity and lower daytime activity, was associated with higher BMI. Independent of the duration of rest or activity during the day or night, 24-hour rest and activity patterns from actigraphy provide aggregated measures of activity that associate with BMI in community-dwelling adults.

PMID: 29029250 [PubMed - as supplied by publisher]

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Considerations in the use of MDS research criteria for prodromal Parkinson's in RBD and population cohorts. (Response to letter by Mahlknecht et al).

Considerations in the use of MDS research criteria for prodromal Parkinson's in RBD and population cohorts. (Response to letter by Mahlknecht et al).

Sleep. 2017 Oct 03;:

Authors: Barber TR, Lawton M, Ben-Shlomo Y, Hu MTM

PMID: 29029243 [PubMed - as supplied by publisher]

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A Greater Extent of Insomnia Symptoms and Physician-Recommended Sleep Medication Use Predict Fall Risk in Community-Dwelling Older Adults.

A Greater Extent of Insomnia Symptoms and Physician-Recommended Sleep Medication Use Predict Fall Risk in Community-Dwelling Older Adults.

Sleep. 2017 Oct 03;:

Authors: Chen TY, Lee S, Buxton OM

Abstract
Study Objectives: Cross-sectional studies suggest that insomnia symptoms are associated with falls in later life. This longitudinal study examines the independent and interactive effects of the extent of insomnia symptoms (i.e., multiple co-existing insomnia symptoms) and sleep medications on fall risk over a 2-year follow-up among community-dwelling older adults.
Methods: Using data from the Health and Retirement Study (2006-2014, N = 6882, Mage = 74.5 years ± 6.6 years), we calculated the extent of insomnia symptoms (range = 0-4) participants reported (i.e., trouble falling asleep, waking up during the night, waking up too early, and not feeling rested). At each wave, participants reported recent sleep medications use and falls since the last wave, and were evaluated for balance and walking speed.
Results: A greater burden of insomnia symptoms and using physician-recommended sleep medications at baseline independently predicted falling after adjusting for known risk factors of falling. The effects of insomnia symptoms on fall risk differed by sleep medications use. The extent of insomnia symptoms exhibited a positive, dose-response relation with risk of falling among those not using sleep medications. Older adults using physician-recommended sleep medications exhibited a consistently higher fall risk irrespective of the extent of insomnia symptoms.
Conclusions: The number of insomnia symptoms predicts 2-year fall risk in older adults. Taking physician-recommended sleep medications increases the risks for falling in older adults, irrespective of the presence of insomnia symptoms. Future efforts should be directed toward treating insomnia symptoms, and managing and selecting sleep medications effectively to decrease the risk of falling in older adults.

PMID: 29029240 [PubMed - as supplied by publisher]

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What does the sleeping brain say? Syntax and semantics of sleep talking in healthy subjects and in parasomnia patients.

What does the sleeping brain say? Syntax and semantics of sleep talking in healthy subjects and in parasomnia patients.

Sleep. 2017 Oct 05;:

Authors: Arnulf I, Uguccioni G, Gay F, Baldayrou E, Golmard JL, Gayraud F, Devevey A

Abstract
Objectives: Speech is a complex function in humans, but the linguistic characteristics of sleep talking are unknown. We analyzed sleep-associated speech in adults, mostly (92%) during parasomnias.
Methods: The utterances recorded during night-time video-polysomnography were analyzed for number of words, propositions and speech episodes, frequency, gaps and pauses (denoting turn-taking in the conversation), lemmatization, verbosity, negative/imperative/interrogative tone, first/second person, politeness and abuse.
Results: The 232 subjects (aged 49.5 ± 20 y old; 41% women; 129 with rapid eye movement [REM] sleep behavior disorder and 87 with sleepwalking/sleep terrors, 15 healthy subjects and 1 patient with sleep apnea speaking in non-REM sleep) uttered 882 speech episodes, containing 59% non-verbal utterance (mumbles, shouts, whispers, laughs) and 3349 understandable words. The most frequent word was "No": negations represented 21.4% of clauses (more in non-REM sleep). Interrogations were found in 26% of speech episodes (more in non-REM sleep), and subordinate clauses were found in 12.9% of speech episode. As many as 9.7% of clauses contained profanities (more in non-REM sleep). Verbal abuse lasted longer in REM sleep and was mostly directed towards insulting or condemning someone, whereas swearing predominated in non-REM sleep. Men sleep-talked more than women and used a higher proportion of profanities. Apparent turn-taking in the conversation respected the usual language gaps.
Conclusions: Sleep talking parallels awake talking for syntax, semantics and turn- taking in conversation, suggesting that the sleeping brain can function at a high level. Language during sleep is mostly a familiar, tensed conversation with inaudible others, suggestive of conflicts.

PMID: 29029239 [PubMed - as supplied by publisher]

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Thyroid High-Impact Articles

FREE ACCESS through October 25, 2017.
Read now:

Latest Impact Factor: 5.515
The Official Journal of: American Thyroid Association

Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis
Fereidoun Azizi, Ramin Malboosbaf

Do Lower-Risk Thyroid Cancer Patients Who Live in Regions with More Aggressive Treatments Have Better Outcomes?
Stephen F. Hall, Jonathan Irish, Patti Groome, Rebecca Griffiths, David Hurlbut

Identification of Two Distinct Molecular Subtypes of Non-Invasive Follicular Neoplasm with Papillary-Like Nuclear Features by Digital RNA Counting
Riccardo Giannini, Clara Ugolini, Anello Marcello Poma, Maria Urpì, Cristina Niccoli, Rossella Elisei, Massimo Chiarugi, Paolo Vitti, Paolo Miccoli, Fulvio Basolo

¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography May Exclude Malignancy in Sonographically Suspicious and Scintigraphically Hypofunctional Thyroid Nodules and Reduce Unnecessary Thyroid Surgeries
Marcus Ruhlmann, Jürgen Ruhlmann, Rainer Görges, Ken Herrmann, Gerald Antoch, Hans-Wilhelm Keller, Verena Ruhlmann

Recovery of 3-Iodothyronamine and Derivatives in Biological Matrixes: Problems and Pitfalls
Leonardo Lorenzini, Sandra Ghelardoni, Alessandro Saba, Ginevra Sacripanti, Grazia Chiellini, Riccardo Zucchi

The post <i>Thyroid</i> High-Impact Articles appeared first on American Thyroid Association.

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Scaling of the ankle extensor muscle-tendon units and the biomechanical implications for bipedal hopping locomotion in the post-pouch kangaroo Macropus fuliginosus

Abstract

Bipedal hopping is used by macropods, including rat-kangaroos, wallabies and kangaroos (superfamily Macropodoidea). Interspecific scaling of the ankle extensor muscle-tendon units in the lower hindlimbs of these hopping bipeds shows that peak tendon stress increases disproportionately with body size. Consequently, large kangaroos store and recover more strain energy in their tendons, making hopping more efficient, but their tendons are at greater risk of rupture. This is the first intraspecific scaling analysis on the functional morphology of the ankle extensor muscle-tendon units (gastrocnemius, plantaris and flexor digitorum longus) in one of the largest extant species of hopping mammal, the western grey kangaroo Macropus fuliginosus (5.8–70.5 kg post-pouch body mass). The effective mechanical advantage of the ankle extensors does not vary with post-pouch body mass, scaling with an exponent not significantly different from 0.0. Therefore, larger kangaroos balance rotational moments around the ankle by generating muscle forces proportional to weight-related gravitational forces. Maximum force is dependent upon the physiological cross-sectional area of the muscle, which we found scales geometrically with a mean exponent of only 0.67, rather than 1.0. Therefore, larger kangaroos are limited in their capacity to oppose large external forces around the ankle, potentially compromising fast or accelerative hopping. The strain energy return capacity of the ankle extensor tendons increases with a mean exponent of ~1.0, which is much shallower than the exponent derived from interspecific analyses of hopping mammals (~1.4–1.9). Tendon safety factor (ratio of rupture stress to estimated peak hopping stress) is lowest in the gastrocnemius (< 2), and it decreases with body mass with an exponent of −0.15, extrapolating to a predicted rupture at 160 kg. Extinct giant kangaroos weighing 250 kg could therefore not have engaged in fast hopping using 'scaled-up' lower hindlimb morphology of extant western grey kangaroos.

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Lipid signaling affects primary fibroblast collective migration and anchorage in response to stiffness and microtopography

ABSTRACT

Cell migration is regulated by several mechanotransduction pathways, which consist of sensing and converting mechanical microenvironmental cues to internal biochemical cellular signals, such as protein phosphorylation and lipid signaling. While there has been significant progress in understanding protein changes in the context of mechanotransduction, lipid signaling is more difficult to investigate. In this study, physical cues of stiffness (10 kPa, 100 kPa, 400 kPa, and glass), and microrod or micropost topography were manipulated in order to reprogram primary fibroblasts and assess the effects of lipid signaling on the actin cytoskeleton. In an in vitro wound closure assay, primary cardiac fibroblast migration velocity was significantly higher on soft polymeric substrata. Modulation of PIP2 availability through neomycin treatment nearly doubled migration velocity on 10 kPa substrata, with significant increases on all stiffnesses. The distance between focal adhesions and the lamellar membrane (using wortmannin treatment to increase PIP2 via PI3K inhibition) was significantly shortest compared to untreated fibroblasts grown on the same surface. PIP2 localized to the leading edge of migrating fibroblasts more prominently in neomycin-treated cells. The membrane-bound protein, lamellipodin, did not vary under any condition. Additionally, fifteen micron-high micropost topography, which blocks migration, concentrates PIP2 near to the post. Actin dynamics within stress fibers, measured by fluorescence recovery after photobleaching, was not significantly different with stiffness, microtopography, nor with drug treatment. PIP2-modulating drugs delivered from microrod structures also affected migration velocity. Thus, manipulation of the microenvironment and lipid signaling regulatory drugs might be beneficial in improving therapeutics geared toward wound healing. This article is protected by copyright. All rights reserved

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Involvement of the Nrf2/HO-1/CO axis and therapeutic intervention with the CO-Releasing Molecule CORM-A1, in a murine model of Autoimmune Hepatitis

Abstract

Concanavalin A (ConA)-induced hepatitis is an experimental model of human autoimmune hepatitis induced in rodents by i.v. injection of Con A. The disease is characterized by increase in serum levels of transaminases and massive immune infiltration of the livers. Type 1, type 2 and type 17 cytokines play a pathogenic role in the development of ConA-induced hepatitis. To understand further the immunoregulatory mechanisms operating in the development and regulation of ConA-induced hepatitis, we have evaluated the role of the anti-inflammatory pathway Nrf2/HO-1/CO (Nuclear Factor E2-related Factor 2/Heme Oxygenase-1/Carbon Monoxide) in this condition and determined whether the in vivo administration of CO via the CO-releasing molecule (CORM) CORM-A1, influences serological and histological development of Con-A-induced hepatitis. We have firstly evaluated in silico the genes belonging to the Nrf2/HO-1/CO pathway that are involved in the pathogenesis of autoimmune hepatitis (AIH). The data obtained from the in silico study demonstrate that a significant number of genes modulated in the liver of ConA-challenged mice belong to the Nrf2 pathway; on the other hand, the administration of CORM-A1 determines an improvement in several sero-immunological and histological parameters, and it is able to modulate genes identified by the in silico analysis. Collectively, our data indicate that the Nrf2/HO-1/CO pathway is fundamental for the regulation of the immune responses, and that therapeutic intervention aimed at its modulation by CORM-A1 may represent a valuable strategy to be considered for the treatment of autoimmune hepatitis in humans. This article is protected by copyright. All rights reserved

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Effect of Mono–(2–Ethylhexyl) Phthalate(MEHP) on Proliferation of and Steroid Hormone Synthesis in Rat Ovarian Granulosa Cells In Vitro

Abstract

This study aimed to examine the proliferation of and secretion by rat ovarian granulosa cells (GCs) treated with mono–(2–ethylhexyl) phthalate (MEHP). Ovarian GCs were incubated with MEHP at concentration of 0, 25, 50, 100, and 200µM for 24 hours. Cell viability was determined using the MTT Cell Proliferation Assay. Progesterone and estradiol production was evaluated by radioimmunoassay (RIA) and the expression of FSHR, PR, and ER was measured by immunocytochemistry. StAR, P450scc, 3β-HSD, 17β-HSD, and P₄₅₀arom mRNA levels were determined by RT–PCR. MEHP markedly attenuated proliferation of GCs, increased expression of sex hormone receptors and key enzymes in progesterone production, and stimulated steroid hormone secretion.The result of these analyses demonstrates that MEHP exposure of GCs may have effects on rat ovarian functions. This article is protected by copyright. All rights reserved

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Orthodontic treatment for Class II division 2 malocclusion: No randomised trial evidence

This Cochrane review of orthodontic treatment for class II div 2 malocclusion updates the previous 2006 version. No RCTs or CCTs were identified so It is not possible to provide any evidence-based guidance to recommend or discourage any type of orthodontic treatment to correct Class II division 2 malocclusion in children.

The post Orthodontic treatment for Class II division 2 malocclusion: No randomised trial evidence appeared first on National Elf Service.

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Structurally Novel Antiestrogens Elicit Differential Responses from Constitutively Active Mutant Estrogen Receptors in Breast Cancer Cells and Tumors

Many estrogen receptor α (ERα)–positive breast cancers develop resistance to endocrine therapy via mutation of ERs whose constitutive activation is associated with shorter patient survival. Because there is now a clinical need for new antiestrogens (AE) against these mutant ERs, we describe here our development and characterization of three chemically novel AEs that effectively suppress proliferation of breast cancer cells and tumors. Our AEs are effective against wild-type and Y537S and D538G ERs, the two most commonly occurring constitutively active ERs. The three new AEs suppressed proliferation and estrogen target gene expression in WT and mutant ER-containing cells and were more effective in D538G than in Y537S cells and tumors. Compared with WT ER, mutants exhibited approximately 10- to 20-fold lower binding affinity for AE and a reduced ability to be blocked in coactivator interaction, likely contributing to their relative resistance to inhibition by AE. Comparisons between mutant ER–containing MCF7 and T47D cells revealed that AE responses were compound, cell-type, and ERα-mutant dependent. These new ligands have favorable pharmacokinetic properties and effectively suppressed growth of WT and mutant ER–expressing tumor xenografts in NOD/SCID-γ mice after oral or subcutaneous administration; D538G tumors were more potently inhibited by AE than Y537S tumors. These studies highlight the differential responsiveness of the mutant ERs to different AEs and make clear the value of having a toolkit of AEs for treatment of endocrine therapy–resistant tumors driven by different constitutively active ERs. Cancer Res; 77(20); 5602–13. ©2017 AACR.

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Cancer Self-Defense: An Immune Stealth

The hurdles in realizing successful cancer immunotherapy stem from the fact that cancer patients are either refractory to immune response and/or develop resistance. Here, we propose that these phenomena are due, in part, to the deployment/secretion of a "decoy flare," for example, anomalous cancer-associated antigens by the tumor cells. The cancer secretome, which resembles the parent cell make-up, is composed of soluble macromolecules (proteins, glycans, lipids, DNAs, RNAs, etc.) and insoluble vesicles (exosomes), thus hindering cancer detection/recognition by immunotherapeutic agents, resulting in a "cancer-stealth" effect. Immunotherapy, or any treatment that relies on antigens' expression/function, could be improved by the understanding of the properties of the cancer secretome, as its clinical evaluation may change the therapeutic landscape. Cancer Res; 77(20); 5441–4. ©2017 AACR.

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Highlights from Recent Cancer Literature

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The Rac GTPase in Cancer: From Old Concepts to New Paradigms

Rho family GTPases are critical regulators of cellular functions that play important roles in cancer progression. Aberrant activity of Rho small G-proteins, particularly Rac1 and their regulators, is a hallmark of cancer and contributes to the tumorigenic and metastatic phenotypes of cancer cells. This review examines the multiple mechanisms leading to Rac1 hyperactivation, particularly focusing on emerging paradigms that involve gain-of-function mutations in Rac and guanine nucleotide exchange factors, defects in Rac1 degradation, and mislocalization of Rac signaling components. The unexpected pro-oncogenic functions of Rac GTPase-activating proteins also challenged the dogma that these negative Rac regulators solely act as tumor suppressors. The potential contribution of Rac hyperactivation to resistance to anticancer agents, including targeted therapies, as well as to the suppression of antitumor immune response, highlights the critical need to develop therapeutic strategies to target the Rac pathway in a clinical setting. Cancer Res; 77(20); 5445–51. ©2017 AACR.

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CD73 Promotes Resistance to HER2/ErbB2 Antibody Therapy

Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective, randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression were associated significantly with poor clinical outcome. In contrast, high levels of PD-1 and PD-L1 were associated with improved clinical outcome. In immunocompetent mouse models of HER2/ErbB2–driven breast cancer, CD73 expression by tumor cells and host cells significantly suppressed immune-mediated responses mediated by anti-ErbB2 mAb. Furthermore, anti-CD73 mAb therapy enhanced the activity of anti-ErbB2 mAb to treat engrafted or spontaneous tumors as well as lung metastases. Gene ontology enrichment analysis from gene-expression data revealed a positive association of CD73 expression with extracellular matrix organization, TGFβ genes, epithelial-to-mesenchymal transition (EMT) transcription factors and hypoxia-inducible-factor (HIF)-1 gene signature. Human mammary cells treated with TGFβ or undergoing EMT upregulated CD73 cell-surface expression, confirming roles for these pathways. In conclusion, our findings establish CD73 in mediating resistance to trastuzumab and provide new insights into how CD73 is regulated in breast cancer. Cancer Res; 77(20); 5652–63. ©2017 AACR.

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HIF-2{alpha} Promotes Dissemination of Plasma Cells in Multiple Myeloma by Regulating CXCL12/CXCR4 and CCR1

Disease progression and relapse in multiple myeloma is dependent on the ability of the multiple myeloma plasma cells (PC) to reenter the circulation and disseminate throughout the bone marrow. Increased bone marrow hypoxia is associated with increased recirculation of multiple myeloma PCs. Accordingly, we hypothesized that during chronic hypoxia, activation of HIF-2α may overcome the bone marrow retention signal provided by stromal-derived CXCL12, thereby enabling dissemination of multiple myeloma PCs. Here we demonstrate that HIF-2α upregulates multiple myeloma PC CXCL12 expression, decreasing migration toward CXCL12 and reducing adhesion to mesenchymal stromal cells in vitro. We also found that HIF-2α strongly induced expression of the chemokine receptor CCR1 in multiple myeloma PCs. CCR1 activation potently induces multiple myeloma PC migration toward CCL3 while abrogating the multiple myeloma PC migratory response to CXCL12. In addition, increased CCR1 expression by multiple myeloma PCs conferred poor prognosis in newly diagnosed multiple myeloma patients and was associated with an increase in circulating multiple myeloma PCs in these patients. Taken together, our results suggest a role for hypoxia-mediated CCR1 upregulation in driving the egress of multiple myeloma PCs from the bone marrow. Targeting CCR1 may represent a novel strategy to prevent dissemination and overt relapse in multiple myeloma. Cancer Res; 77(20); 5452–63. ©2017 AACR.

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