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Introduction The demographic shift in the age profile of the UK is now well established. Older people have more complex requirements to maintain their oral health and appropriate training is required to provide good-quality oral and dental care. This research aimed to review the training in gerodontology currently being provided to undergraduate dental and dental hygiene therapy (DHT) students in the UK.Methods Quantitative data were generated through completion of an online questionnaire, emailed to the directors of dental education in each of the UK dental (n = 16) and DHT schools (n = 21). Data were analysed using IBM SPSS Statistics V26.Results There was a response rate of 37.5% from dental schools and 61.9% from DHT schools. Although gerodontology was being taught in every school that responded, it was only a standalone course in 16.7% of dental schools and 7.7% of DHT schools that responded. While all respondents reported a theoretical component, only 50% of dental schools and 53.8% of DHT schools reported providing clinical experience. Moreover, 33.3% of dental schools and 15.4% of DHT schools reported closely following the European curriculum guidelines in gerodontology.Conclusions The current training in gerodontology is not standardised across either dental or DHT schools in the UK and there seems to be a lack of awareness of the recommended European guidelines. The findings from this research demonstrate that future improvements in gerodontology training are still required for this to be achieved.

BackgroundWith the surge of new SARS-CoV-2 variants, countries have begun offering COVID-19 vaccine booster doses to high-risk groups and, more recently, to the adult population in general. However, uncertainty remains over how long primary vaccination series remain effective, the ideal timing for booster doses, and the safety of heterologous booster regimens. We aimed to investigate COVID-19 primary vaccine series effectiveness and its waning, and the safety and effectiveness of booster doses, in a UK community setting.MethodsWe used SARS-CoV-2 positivity rates in individuals from a longitudinal, prospective, community-based study (ZOE COVID Study), in which data were self-reported through an app, to assess the effectiveness of three COVID-19 vaccines (ChAdOx1 nCov19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNtech], and mRNA1273 [Moderna]) against infection in the 8 months after completion of primary vaccination series. In individuals receiving boosters, we investigated vaccine effectiveness and reactogenicity, by assessing 16 self-reported systemic and localised side-effects. We used multivariate Poisson regression models adjusting for confounders to estimate vaccine effectiveness.FindingsWe included 620 793 participants who received two vaccine doses (204 731 [33·0%] received BNT162b2, 405 239 [65·3%] received ChAdOx1 nCoV-19, and 10 823 [1·7%] received mRNA-1273) and subsequently had a SARS-CoV-2 test result between May 23 (chosen to exclude the period of alpha [B.1.1.7] variant dominance) and Nov 23, 2021. 62 172 (10·0%) vaccinated individuals tested positive for SARS-CoV-2 and were compared with 40 345 unvaccinated controls (6726 [16·7%] of whom tested positive). Vaccine effectiveness waned after the second dose: at 5 months, BNT162b2 effectiveness was 82·1% (95% CI 81·3–82·9), ChAdOx1 nCoV-19 effectiveness was 75·7% (74·9–76·4), and mRNA-1273 effectiveness was 84·3% (81·2–86·9). Vaccine effectiveness decreased more among individuals aged 55 years or older and among those with comorbidities. 135 932 individuals aged 55 years or older received a booster (2123 [1·6%] of whom tested positive). Vaccine effectiveness for booster doses in 0–3 months after BNT162b2 primary vaccination was higher than 92·5%, and effectiveness for heterologous boosters after ChAdOx1 nCoV-19 was at least 88·8%. For the booster reactogenicity analysis, in 317 011 participants, the most common systemic symptom was fatigue (in 31 881 [10·1%] participants) and the most common local symptom was tenderness (in 187 767 [59·2%]). Systemic side-effects were more common for heterologous schedules (32 632 [17·9%] of 182 374) than for homologous schedules (17 707 [13·2%] of 134 637; odds ratio 1·5, 95% CI 1·5–1·6, pInterpretationAfter 5 months, vaccine effectiveness remained high among individuals younger than 55 years. Booster doses restore vaccine effectiveness. Adverse reactions after booster doses were similar to those after the second dose. Homologous booster schedules had fewer reported systemic side-effects than heterologous boosters.FundingWellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, Medical Research Council

Background: Understanding the dynamics of the COVID-19 pandemic and evaluating the efficacy of control measures requires knowledge of the number of infections over time. This number, however, often differs from the number of confirmed cases because of a large fraction of asymptomatic infections and different testing strategies. Methods: This study uses death count statistics, age-dependent infection fatality risks, and stochastic modeling to estimate the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among adults (aged 20 years or older) in 165 countries over time, from early 2020 until June 25, 2021. The accuracy of the approach is confirmed through comparison with previous nationwide seroprevalence surveys. Results: The estimates presented reveal that the fraction of infections that are detected vary widely over time and between countries, and hence confirmed cases alone often yield a false picture of the pandemic. As of June 25, 2021, the nationwide cumulative fraction of SARS-CoV-2 infections (cumulative infections relative to population size) was estimated as 98% (95% confidence interval [CI] 93–100%) for Peru, 83% (95% CI 61–94%) for Brazil, and 36% (95% CI 23–61%) for the United States. Conclusions: The time-resolved estimates presented expand the possibilities to study the factors that influenced and still influence the pandemic’s progression in 165 countries.

Postprandial insulinaemia, triglyceridaemia and measures of inflammation are thought to be more closely associated with cardiovascular risk than fasting measures. Although hypertension is associated with altered fasting metabolism, it is unknown as to what extent postprandial lipaemic and inflammatory metabolic responses differ between hypertensive and normotensive individuals. Linear models adjusting for age, sex, body mass index (BMI), visceral fat mass (VFM) and multiple testing (false discovery rate), were used to investigate whether hypertensive cases and normotensive controls had different fasting and postprandial (in response to two standardised test meal challenges) lipaemic, glycaemic, insulinaemic, and inflammatory (glycoprotein acetylation (GlycA)) responses in 989 participants from the ZOE PREDICT-1 nutritional intervention study. Compared to normotensive controls, hypertensive individuals had significantly higher fasting and postprandial insulin, triglycerides, and markers of inflammation after adjusting for age, sex, and BMI (effect size: Beta (Standard Error) ranging from 0.17 (0.08), p = 0.04 for peak insulin to 0.29 (0.08), p = 4.4 × 10−4 for peak GlycA). No difference was seen for postprandial glucose. When further adjusting for VFM effects were attenuated. Causal mediation analysis suggests that 36% of the variance in postprandial insulin response and 33.8% of variance in postprandial triglyceride response were mediated by VFM. Hypertensive individuals have different postprandial insulinaemic and lipaemic responses compared to normotensive controls and this is partially mediated by visceral fat mass. Consequently, reducing VFM should be a key focus of health interventions in hypertension. Trial registration: The ClinicalTrials.gov registration identifier is NCT03479866.

ImportanceWearing a face mask in school can reduce SARS-CoV-2 transmission but it may also lead to increased hand-to-face contact, which in turn could increase infection risk through self-inoculation.ObjectiveTo evaluate the effect of wearing a face mask on hand-to-face contact by children while at school.Design, Setting, and ParticipantsThis prospective randomized clinical trial randomized students from junior kindergarten to grade 12 at 2 schools in Toronto, Ontario, Canada, during August 2020 in a 1:1 ratio to either a mask or control class during a 2-day school simulation. Classes were video recorded from 4 angles to accurately capture outcomes.InterventionsParticipants in the mask arm were instructed to bring their own mask and wear it at all times. Students assigned to control classes were not required to mask at any time (grade 4 and lower) or in the classroom where physical distancing could be maintained (grade 5 and up).Main Outcomes and MeasuresThe primary outcome was the number of hand-to-face contacts per student per hour on day 2 of the simulation. Secondary outcomes included hand-to-mucosa contacts and hand-to-nonmucosa contacts. A mixed Poisson regression model was used to derive rate ratios (RRs), adjusted for age and sex with a random intercept for class with bootstrapped 95% CIs.ResultsA total of 174 students underwent randomization and 171 students (mask group, 50.6% male; control group, 52.4% male) attended school on day 2. The rate of hand-to-face contacts did not differ significantly between the mask and the control groups (88.2 vs 88.7 events per student per hour; RR, 1.00; 95% CI, 0.78-1.28; P = >.99). When compared with the control group, the rate of hand-to-mucosa contacts was significantly lower in the mask group (RR, 0.12; 95% CI, 0.07-0.21), while the rate of hand-to-nonmucosa contacts was higher (RR, 1.40; 95% CI, 1.08-1.82).Conclusions and RelevanceIn this clinical trial of simulated school attendance, hand-to-face contacts did not differ among students required to wear face masks vs students not required to wear face masks; however, hand-to-mucosa contracts were lower in the face mask group. This suggests that mask wearing is unlikely to increase infection risk through self-inoculation.Trial RegistrationClinicalTrials.gov Identifier: NCT04531254

Background Higher education tends to focus on academic writing only, instead of emphasizing that professional texts are also used as a basis for communication in contexts with a variety of participators. When it comes to clinical notes, research is scarce and focused on technology and informatics. Therefore, the aim was to explore dental students’ clinical notes, and specifically which aspects of the clinical notes characterizes clinical notes that are not sufficient enough for professional purposes. Methods The object of analysis was the student’s written completion of a teacher constructed protocol regarding oral mucosa, the dental apparatus including pathology on tooth level, oral hygiene, and a validated international clinical examination protocol of the temporomandibular region. The study was framed within the New Literacy Studies approach, and the clinical notes were analyzed using thematic analysis. Results Within the clinical notes three themes were identified; a) familiar content; b) familiar content in new context; and c) new content. The forms of notes could refer to either categorizational clinical notes or descriptive clinical notes. Most students were able to write acceptable clinical notes when the content was familiar, but as soon as the familiar content was in a new context the students had difficulties to write acceptable notes. When it comes to descriptive notes students suffered difficulties to write acceptable notes both when it came to familiar content, or familiar content in a new context. Conclusions Taken together, the results indicate that students have difficulties writing acceptable notes when they are novices to the content or context, making their notes either insufficient, too short or even wrong for professional purposes. With this in mind, this study suggests that there is a need to strengthen the demands on sufficient professional quality in clinical notes and focus on clinical notes already in the early stages of the different medical educations.

Aims/hypothesis The gut microbiome is hypothesised to be related to insulin resistance and other metabolic variables. However, data from population-based studies are limited. We investigated associations between serologic measures of metabolic health and the gut microbiome in the Northern Finland Birth Cohort 1966 (NFBC1966) and the TwinsUK cohort. Methods Among 506 individuals from the NFBC1966 with available faecal microbiome (16S rRNA gene sequence) data, we estimated associations between gut microbiome diversity metrics and serologic levels of HOMA for insulin resistance (HOMA-IR), HbA1c and C-reactive protein (CRP) using multivariable linear regression models adjusted for sex, smoking status and BMI. Associations between gut microbiome diversity measures and HOMA-IR and CRP were replicated in 1140 adult participants from TwinsUK, with available faecal microbiome (16S rRNA gene sequence) data. For both cohorts, we used general linear models with a quasi-Poisson distribution and Microbiome Regression-based Kernel Association Test (MiRKAT) to estimate associations of metabolic variables with alpha- and beta diversity metrics, respectively, and generalised additive models for location scale and shape (GAMLSS) fitted with the zero-inflated beta distribution to identify taxa associated with the metabolic markers. Results In NFBC1966, alpha diversity was lower in individuals with higher HOMA-IR with a mean of 74.4 (95% CI 70.7, 78.3) amplicon sequence variants (ASVs) for the first quartile of HOMA-IR and 66.6 (95% CI 62.9, 70.4) for the fourth quartile of HOMA-IR. Alpha diversity was also lower with higher HbA1c (number of ASVs and Shannon’s diversity, p p = 0.003, respectively) and higher CRP (number of ASVs, p = 0.025), even after adjustment for BMI and other potential confounders. In TwinsUK, alpha diversity measures were also lower among participants with higher measures of HOMA-IR and CRP. When considering beta diversity measures, we found that microbial community profiles were associated with HOMA-IR in NFBC1966 and TwinsUK, using multivariate MiRKAT models, with binomial deviance dissimilarity p values of Prevotella and Blautia were associated with HOMA-IR in both cohorts. Conclusions/interpretation Overall, higher levels of HOMA-IR, CRP and HbA1c were associated with lower microbiome diversity in both the NFBC1966 and TwinsUK cohorts, even after adjustment for BMI and other variables. These results from two distinct population-based cohorts provide evidence for an association between metabolic variables and gut microbial diversity. Further experimental and mechanistic insights are now needed to provide understanding of the potential causal mechanisms that may link the gut microbiota with metabolic health. Graphical abstract

Funder: Health Education England Academic Clinical Lectureship, Funder: National Institute for Health Research (NIHR), OBJECTIVES: uncertainty pervades the complex illness trajectories experienced by older adults with multimorbidity. Uncertainty is experienced by older people, their informal carers and professionals providing care, yet is incompletely understood. We aimed to identify and synthesise systematically the experience of uncertainty in advanced multimorbidity from patient, carer and professional perspectives. DESIGN: systematic literature review of published and grey qualitative literature from 9 databases (Prospero CRD 42021227480). PARTICIPANTS: older people with advanced multimorbidity, and informal carers/professionals providing care to this group. Exclusion criteria: early multimorbidity, insufficient focus on uncertainty. ANALYSIS: weight-of-evidence assessment was used to appraise included articles. We undertook thematic synthesis of multi-perspective experiences and response to uncertainty. RESULTS: from 4,738 unique search results, we included 44 articles relating to 40 studies. 22 focused on patient experiences of uncertainty (n = 460), 15 on carer experiences (n = 197), and 19 on health professional experiences (n = 490), with 10 exploring multiple perspectives. We identified a shared experience of 'Total Uncertainty' across five domains: 'appraising and managing multiple illnesses'; 'fragmented care and communication'; 'feeling overwhelmed'; 'uncertainty of others' and 'continual change'. Participants responded to uncertainty by either active (addressing, avoiding) or passive (accepting) means. CONCLUSIONS: the novel concept of 'Total Uncertainty' represents a step change in our understanding of illness experience in advanced multimorbidity. Patients, carers and health professionals experienced uncertainty in similar domains, suggesting a shared understanding is feasible. The domains of total uncertainty form a useful organising framework for health professionals caring for older adults with multimorbidity., SE is funded by a Health Education England Academic Clinical Lectureship SB is part funded by the National Institute for Health Research (NIHR) Applied Research Collaboration East of England (ARC EoE) programme. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. SH is jointly funded by The Dunhill Medical Trust and British Geriatrics Society [Grant ref. JBGS20\5]

Purpose Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. Methods Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. Results We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. Conclusion This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society.

Viral phylogenies provide crucial information on the spread of infectious diseases, and many studies fit mathematical models to phylogenetic data to estimate epidemiological parameters such as the effective reproduction ratio (Re) over time. Such phylodynamic inferences often complement or even substitute for conventional surveillance data, particularly when sampling is poor or delayed. It remains generally unknown, however, how robust phylodynamic epidemiological inferences are, especially when there is uncertainty regarding pathogen prevalence and sampling intensity. Here we use recently developed mathematical techniques to fully characterize the information that can possibly be extracted from serially collected viral phylogenetic data, in the context of the commonly used birth-death-sampling model. We show that for any candidate epidemiological scenario, there exist a myriad of alternative, markedly different and yet plausible “congruent” scenarios that cannot be distinguished using phylogenetic data alone, no matter how large the dataset. In the absence of strong constraints or rate priors across the entire study period, neither maximum-likelihood fitting nor Bayesian inference can reliably reconstruct the true epidemiological dynamics from phylogenetic data alone; rather, estimators can only converge to the “congruence class” of the true dynamics. We propose concrete and feasible strategies for making more robust epidemiological inferences from viral phylogenetic data.

The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the extent to which two isocaloric dietary interventions—Mediterranean (M) and high protein (HP)—improved metabolic parameters. Obese women were assigned to one of the following dietary sequences: M–HP or HP–M. Cardiometabolic parameters, body weight, glucose monitoring and gut microbiome composition were assessed. Sixteen women completed the study. Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = −6.98 (−12.30, −1.65) µIU/mL, p = 0.01; HOMA-IR: −1.78 (95% CI: −3.03, −0.52), p = 9 × 10−3); and (ii) improving glycemic variability (−3.13 (−4.60, −1.67) mg/dL, p = 4 × 10−4), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera Coprococcus and Lachnoclostridium, previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.

To investigate the relationship between dietary intake of niacin (water-soluble form of vitamin BThis cross-sectional study examined the association between daily niacin intake and RNFL thickness in three large population-based cohorts with varied age differences. RNFL thickness was extracted from optical coherence tomography data; energy-adjusted niacin intake was estimated from food frequency questionnaires. Linear mixed-effects models were utilised to examine the association between RNFL thickness and energy-adjusted niacin intake. Three separate analyses were conducted, with niacin treated as a continuous, a categorical (quartiles) or a dichotomous (above/below Australian recommended daily intake) variable.In total, 4937 subjects were included in the study [Raine Study Gen2, n = 1204, median age 20; Busselton Healthy Ageing Study (BHAS), n = 1791, median age 64; TwinsUK, n = 1942, median age 64). When analysed as a continuous variable, there was no association between RNFL thickness and niacin intake in any of the three cohorts (95% CI β: Raine Study Gen 2, -0.174 to 0.074; BHAS, -0.066 to 0.078; TwinsUK -0.435 to 0.350). Similar findings were observed with quartiles of niacin intake and for niacin intakes above or below Australian recommended daily intake levels in all three cohorts.Dietary intake of niacin from a standard diet does not appear to be associated with age-related RNFL thinning in healthy eyes. Supraphysiological doses of niacin may be required for therapeutic effect in the retina.

uncertainty pervades the complex illness trajectories experienced by older adults with multimorbidity. Uncertainty is experienced by older people, their informal carers and professionals providing care, yet is incompletely understood. We aimed to identify and synthesise systematically the experience of uncertainty in advanced multimorbidity from patient, carer and professional perspectives.systematic literature review of published and grey qualitative literature from 9 databases (Prospero CRD 42021227480).older people with advanced multimorbidity, and informal carers/professionals providing care to this group. Exclusion criteria: early multimorbidity, insufficient focus on uncertainty.weight-of-evidence assessment was used to appraise included articles. We undertook thematic synthesis of multi-perspective experiences and response to uncertainty.from 4,738 unique search results, we included 44 articles relating to 40 studies. 22 focused on patient experiences of uncertainty (n = 460), 15 on carer experiences (n = 197), and 19 on health professional experiences (n = 490), with 10 exploring multiple perspectives. We identified a shared experience of 'Total Uncertainty' across five domains: 'appraising and managing multiple illnesses'; 'fragmented care and communication'; 'feeling overwhelmed'; 'uncertainty of others' and 'continual change'. Participants responded to uncertainty by either active (addressing, avoiding) or passive (accepting) means.the novel concept of 'Total Uncertainty' represents a step change in our understanding of illness experience in advanced multimorbidity. Patients, carers and health professionals experienced uncertainty in similar domains, suggesting a shared understanding is feasible. The domains of total uncertainty form a useful organising framework for health professionals caring for older adults with multimorbidity.

Most gliomas are invasive tumors formed from glial cells and associated with high mortality rates. In this study, we characterized four glioma cell lines of varying degree of aggressiveness (H4, SW1088, A172 and U87-MG) in terms of morphology, cytoskeleton organization and stiffness, and evaluated their invasive potential by performing invasion, colony forming and spheroid invasion assays. Cells were divided into two distinct groups: aggressive cell lines (A172 and U87-MG) with more elongated, softer and highly invasive cells and less aggressive cells (H4 and SW088). Interestingly, we found that Ras Suppressor-1 (RSU-1), a cell-matrix adhesion protein involved in cancer cell invasion, was significantly upregulated in more aggressive glioma cells compared to less aggressive. Importantly, RSU-1 silencing had opposing effects on glioma cell invasion depending on their aggressiveness, inhibiting migration and invasion of aggressive cells and promoting those of less aggressive cells. Finally, we found that RSU-1 silencing in aggressive cells led to decreased Signal Transducer and Activator of Transcription6 (STAT6) phosphorylation and Matrix Metalloproteinase13 (MMP13) expression in contrast to less invasive cells. Our study demonstrates that RSU-1 promotes invasion of aggressive glioma cells and inhibits it in the non-aggressive cells, indicating that it could serve as a predictor of gliomas progression.

Robotic rehabilitation of the upper limb has been proved beneficial for people with Multiple Sclerosis (MS). In order to provide task-specific therapy for MS, given its complex impairing nature, it is desired to take advantage of the robots’ ability to move and provide force feedback in generic three-dimensional motions. Previous investigations have shown that hand motion during reaching tasks is piecewise planar, therefore, it is possible to simplify the design of robotic rehabilitation trajectories by confining them on planes oriented in space. To do so, it must first be established whether this natural tendency for tracking a plane during hand movement is affected by the presence of neurological impairment, such as Multiple Sclerosis. This work hypothesizes that in the case of people with MS, planar mapping is not dependent on the resulting impairment. Furthermore, it is investigated whether neurophysiological models such as Fitts’ law and Minimum Jerk Model remain in effect when considering the plane-mapped trajectories and also how these are affected by MS in contrast to natural movement. To test the hypotheses a group of healthy people and a group of people with MS at various stages of the disease have performed reaching tasks in the context of a haptic-interface based Nine-Hole-Pegboard-Test (NHPT) which facilitates the generation of trajectories with various distances and durations in the three-dimensional space. The results suggest that, despite the neurological impairments, the planar adaptation of people with MS is almost as persistent as in the case of healthy people. Furthermore it is shown that Fitts’ law and MJM apply for plane-mapped trajectories and can be utilized in the design of simplified robotic rehabilitation schemes. 62 221 234

Background Music is used to evoke audio analgesia during dental procedures, but it is unknown if experimental pain and music interact. This study aimed to explore the multisensory interaction between contrasting types of music and experimentally induced muscle pain. Methods In 20 healthy women, 0.3 mL sterile hypertonic saline (5.8%) was injected into the masseter muscle during three sessions while contrasting music (classical and black metal) or no music was played in the background. Pain intensity was assessed every 15 seconds with a 0-100 mm visual analogue scale (VAS) until pain subsided. Pain spread (pain drawings), unpleasantness (VAS), anxiety (VAS), and pain quality (McGill Questionnaire) were assessed after the last pain assessment. Results Pain of high intensity was evoked at all sessions with a median (interquartile range) peak pain intensity of 78 (30) in the black metal music, 86 (39) in the classical music, and 77 (30) in the control session. The pain duration was 142 (150) seconds in the black metal music, 135 (150) seconds in the classical music, and 135 (172) seconds in the control session. The corresponding pain-drawing areas were 42 (52), 37 (36), and 44 (34), arbitrary units respectively. There were no differences in any of these variables (Friedman's test; P´s > .368), or in unpleasantness, anxiety, or pain quality between sessions (P´s > .095). Conclusions Experimentally induced muscle pain does not seem to be influenced by contrasting types of background music. Further studies exploring the multisensory integration between music and experimental muscle pain are needed.

Epidemiologic and genomic studies have progressively improved our understanding of the causation of hypertension and the complex relationship with diet and environment. The majority of Mendelian forms of syndromic hypotension and hypertension (HTN) have all been linked to mutations in genes whose encoded proteins regulate salt–water balance in the kidney, supporting the primacy of the kidneys in blood pressure regulation. There are more than 1,477 single nucleotide polymorphisms associated with blood pressure and hypertension and the challenge is establishing a causal role for these variants. Hypertension is a complex multifactorial phenotype and it is likely to be influenced by multiple factors including interactions between diet and lifestyle factors, microbiome, and epigenetics. Given the finite genetic variability that is possible in humans, it is likely that incremental gains from single marker analyses have now plateaued and a greater leap in our understanding of the genetic basis of disease will come from integration of other omics and the interacting environmental factors. In this review, we focus on emerging results from the microbiome and metabolomics and discuss how leveraging these findings may facilitate a deeper understanding of the interrelationships between genomics, diet, and microbial ecology in humans in the causation of essential hypertension.

Background Estimated food records (EFR) are a common dietary assessment method. This investigation aimed to; (1) define the reporting quality of the EFR, (2) characterise acute dietary intake and eating behaviours, (3) describe diet heritability. Methods A total of 1974 one-day EFR were collected from 1858 participants in the TwinsUK cohort between 2012 and 2017. EFR were assessed using a six-point scoring system to determine reporting quality. The frequency and co-occurrence of food items was examined using word clouds and co-occurrence networks. The impact of eating behaviours on weight, BMI and nutrient intake were explored using mixed-effect linear regression models. Finally, diet heritability was estimated using ACE modelling. Results We observed that 75% of EFR are of acceptable reporting quality (score > 5). Black tea and semi-skimmed milk were the most consumed items, on an individual basis (respectively 8.27, 6.25%) and paired (0.21%) as co-occurring items. Breakfast consumption had a significantly (p = 5.99 × 10− 7) greater impact on energy (kcal) (mean 1874.67 (±SD 532.42)) than skipping breakfast (1700.45 (±SD 620.98)), however only length of eating window was significantly associated with body weight (kg) (effect size 0.21 (±SD 0.10), p = 0.05) and BMI (effect size 0.08 (±SD 0.04), p = 0.04) after adjustment for relevant covariates. Lastly, we reported that both length of eating window (h2 = 33%, CI 0.24; 0.41), and breakfast consumption (h2 = 11%, CI 0.02; 0.21) were weakly heritable. Conclusions EFR describing acute dietary intake allow for eating behaviour characterisation and can supplement habitual diet intake assessments. Novel findings of heritability warrant further investigation.

No abstract available.

The nature and quality of feedback provided during the training of healthcare students have been found to influence the progress of students throughout their clinical practice. The use of electronic systems for feedback is becoming more prevalent; but there appears to be an absence of research into the use of these systems with Dental Hygiene and Dental Therapy students (DHDT). The aim of this study was to explore the written, narrative feedback provided by tutors to undergraduate DHDT students on a 3-year BSc programme, using Liftupp - an Information Management System that incorporates electronic feedback mechanisms.The data comprised written, narrative feedback to DHDT students (n = 96) on clinical performance in academic Years Two and Three entered into Liftupp by five clinical tutors (n = 5) over 2 academic years. These feedback comments were subjected to a thematic analysis and matrix queries using NVivo.Ten major themes were identified. Preliminary findings indicated that the constructive "Descriptive" theme was prominent across all tutors, while other constructive themes: "Directive" and "Positive" were linked more to individual tutors. The less constructive themes were infrequent in tutor feedback. In addition, unique feedback profiles for tutors were generated.The analysis of narrative feedback from tutors on Liftupp enables the identification of feedback trends that can be reviewed and shared with tutors to improve the quality of their feedback. In addition, this research can be used to inform tutor training to promote the use of meaningful and effective feedback. Potential further research and limitations have been identified.

BACKGROUND: The SARS-CoV-2 variant of concern, omicron, appears to be less severe than delta. We aim to quantify the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population. METHODS: In this prospective longitudinal observational study, we collected data from participants who were self-reporting test results and symptoms in the ZOE COVID app (previously known as the COVID Symptoms Study App). Eligible participants were aged 16-99 years, based in the UK, with a body-mass index between 15 and 55 kg/m2, had received at least two doses of any SARS-CoV-2 vaccine, were symptomatic, and logged a positive symptomatic PCR or lateral flow result for SARS-CoV-2 during the study period. The primary outcome was the likelihood of developing a given symptom (of the 32 monitored in the app) or hospital admission within 7 days before or after the positive test in participants infected during omicron prevalence compared with those infected during delta prevalence. FINDINGS: Between June 1, 2021, and Jan 17, 2022, we identified 63 002 participants who tested positive for SARS-CoV-2 and reported symptoms in the ZOE app. These patients were matched 1:1 for age, sex, and vaccination dose, across two periods (June 1 to Nov 27, 2021, delta prevalent at >70%; n=4990, and Dec 20, 2021, to Jan 17, 2022, omicron prevalent at >70%; n=4990). Loss of smell was less common in participants infected during omicron prevalence than during delta prevalence (16·7% vs 52·7%, odds ratio [OR] 0·17; 95% CI 0·16-0·19, p

Feedback delivered by teachers to dental students has a profound impact on students' ongoing learning and development. The aim of this study was to investigate changes to feedback practices as a result of the global COVID-19 pandemic and the ensuing challenges to delivering quality dental education.This was a mixed method study. Quantitative data were collected through a bespoke questionnaire delivered to attendees of the Association for Dental Education in Europe (ADEE) annual conference. Qualitative data were collected via four focus groups at the conference, each discussing a particular theme. The questionnaire and conference were delivered online via Gmail and MS Teams, respectively. Quantitative data were analysed descriptively; qualitative data were analysed narratively, and both were triangulated.67 questionnaire responses were received which represented a 26% response rate. Respondents came from 12 different countries within Europe and beyond and reported having a variety of roles in their dental schools. 77.6% (n = 52) respondents indicated they had changed their delivery of feedback due to the pandemic. One-third of respondents reported giving more feedback and 76% (n = 51) increased their quantity of feedback delivered online. The increased incidence of online learning had resulted in a greater emphasis on teaching small groups, increased use of technology, increased emphasis on student centred learning and heightened awareness of changing the style of feedback delivery.The COVID-19 pandemic has enforced rapid changes to the delivery of feedback by teachers to dental students, which could pave the way for a more positive, inclusive, individualistic and effective approach for delivering feedback now and in the future.The COVID-19 pandemic resulted in a significant shift from face-to-face teaching to online tuition, which promoted a need to re-evaluate the best method of delivering feedback to students. The ongoing changes in teaching approaches have a profound impact on clinical skills acquisition for dental students. The quality of the feedback students receive may help to enhance the synergies between theoretical online teaching and hands-on clinical skills acquisition, which has been altered and disrupted due to the ongoing pandemic.

Background: \ud Association studies have identified several biomarkers for blood pressure and hypertension, but a thorough understanding of their mutual dependencies is lacking. By integrating two different high-throughput datasets, biochemical and dietary data, we aim to understand the multifactorial contributors of blood pressure (BP).\ud \ud Methods: \ud We included 4,863 participants from TwinsUK with concurrent BP, metabolomics, genomics, biochemical measures, and dietary data. We used 5-fold cross-validation with the machine learning XGBoost algorithm to identify features of importance in context of one another in TwinsUK (80% training, 20% test). The features tested in TwinsUK were then probed using the same algorithm in an independent dataset of 2,807 individuals from the Qatari Biobank (QBB).\ud \ud Findings: \ud Our model explained 39·2% [4·5%, MAE:11·32 mmHg (95%CI, +/- 0·65)] of the variance in systolic BP (SBP) in TwinsUK. Of the top 50 features, the most influential non-demographic variables were dihomo-linolenate, cis-4-decenoyl carnitine, lactate, chloride, urate, and creatinine along with dietary intakes of total, trans and saturated fat. We also highlight the incremental value of each included dimension. Furthermore, we replicated our model in the QBB [SBP variance explained = 45·2% (13·39%)] cohort and 30 of the top 50 features overlapped between cohorts.\ud \ud Interpretation: \ud We show that an integrated analysis of omics, biochemical and dietary data improves our understanding of their in-between relationships and expands the range of potential biomarkers for blood pressure. Our results point to potentially key biological pathways to be prioritised for mechanistic studies.\ud \ud Funding: \ud Chronic Disease Research Foundation, Medical Research Council, Wellcome Trust, Qatar Foundation.

Introduction: Feedback from teachers to students plays an important role in informing students about the outcome of their assessments. It contributes to students’ ongoing learning. The aim of this study was to investigate dental students’ perceptions of the feedback given to them by their teachers in Europe. Materials & methods: An online questionnaire was completed by dental students throughout Europe in this quantitative study. Data were collected via Google Forms, transferred to an excel spreadsheet and analysed using SPSS software Version 24. Results: 234 students studying in 9 different European countries completed the questionnaire. These students were born in 36 different countries within and beyond Europe. 84% (n = 197) were undergraduate students. 20.3% (n = 48) students reported receiving feedback following summative assessments. 81.2% (n = 190) students reported constructive criticism as their preferred mode of receiving feedback. 11.3% (n = 26) students did not know who delivered the feedback to them. 71% (n = 166) students felt that the feedback they received had a significant impact on their future learning. Conclusion: It would appear that there is some diversity in dental students’ perceptions of: i) who delivers feedback, ii) when feedback is given, iii) the consistency of feedback received, and iv) the style of feedback they preferred compared to that delivered by tutors. Feedback is being provided to dental students in an appropriate and helpful manner, although there is still room for improvement. Students were aware of the significance of feedback and its impact on future learning. Clinical significance: Most European dental students prefer to receive constructive feedback. Feedback was seen to have a significant impact on future learning despite over one in five students not knowing who had delivered their feedback. Feedback following clinical teaching should have a positive effect on students’ skills and motivation to learn.

OBJECTIVES: Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and has been implicated in prevalent hypertension.The aim of this study is to investigate whether the IgG glycome begins to change prior to hypertension diagnosis by analysing the IgG glycome composition in a large population-based female cohort with two independent replication samples. METHODS: We included 989 unrelated cases with incident hypertension and 1628 controls from the TwinsUK cohort (mean follow-up time of 6.3 years) with IgG measured at baseline by ultra-performance liquid chromatography and longitudinal BP measurement available. We replicated our findings in 106 individuals from the 10 001 Dalmatians and 729 from KORA S4. Cox regression mixed models were applied to identify changes in glycan traits preincident hypertension, after adjusting for age, mean arterial pressure, BMI, family relatedness and multiple testing (FDR

Upper eyelid ectropion is rare. When it does occur, the cicatricial subset of upper eyelid ectropion is its most common manifestation. Due to its rarity, little has been published regarding its treatment. Herein, we present the case of a 27-year-old patient who suffered significant left sided facial trauma in a high-velocity motor vehicle accident, resulting in a soft tissue defect in the left lateral supra-orbital region, including loss of the lateral half of the left eyebrow. The defect was left to heal by secondary intention causing severe cicatricial upper eyelid ectropion. Several reconstructive techniques were subsequently utilized including recreating the defect and replacing like with like tissues according to the facial sub-units. Right sided upper eyelid skin was used to replace the deficient left upper eyelid skin and a scalp composite graft was harvested to replace the deficient left lateral eyebrow. Temporary tarsorrhaphy, and steroid injections were used on multiple occasions to counteract the cicatricial forces. Ultimately, permanent lateral tarsorrhaphy and upper eyelid canthopexy was needed to obtain a satisfactory functional and cosmetic result.

Aim This study investigated and evaluated the teaching of occlusion in undergraduate dental schools in the UK and Ireland, the thorough understanding of which would facilitate young graduates to become competent practitioners. Material and methods A mixed-methods approach was employed, with primary data generated and collected by using a cross-sectional, questionnaire-based survey which was followed-up by semi-structured interviews. The hard copy questionnaires enquired about: i) whether occlusion was taught; ii) how long was spent by schools teaching occlusion; iii) what teaching resources were employed; iv) tutors' perceptions of how well prepared for general practice new graduates were; and v) how was knowledge/skill assessed. Follow-up interviews were undertaken with volunteering respondents to triangulate responses. Quantitative data were analysed using descriptive statistics and qualitative data were stored using the Framework Method and analysis using a thematic approach. Results One hundred percent (n = 18) of schools responded to the questionnaire and 66.67% (n = 12) of the schools participated in follow-up interviews. All schools reported that they taught occlusion in their curriculum. Total hours reported teaching occlusion varied from 11 to 310 hours. Twenty-eight percent (n = 5) of respondents reported insufficient time for the teaching of occlusion in the curriculum. There was a marked variation in: i) teaching methods; ii) resources employed; iii) assessment strategies to evaluate competency in occlusion; and iv) how well prepared students were. Thematic analysis of the qualitative data identified several themes: i) variations in teaching pedagogy; ii) use of different resources; iii) variable assessment techniques; iv) evaluation of teaching; and v) barriers to teaching occlusion. Conclusion Recommendations for a coordinated teaching strategy with dedicated oversight to facilitate better student exposure to occlusion and promote student understanding of this topic is suggested.

Introduction: Increasing confidence through learning has the potential to change General Dental Practitioners’ (GDPs) perceptions of clinical practice. By examining how changes in confidence influence the clinical practice of two cohorts of GDPs, during and following an extended period of postgraduate training, we show the importance of confidence to GDPs and that a lack of confidence is a primary reason why GDPs attend postgraduate training courses.Methods: A mixed method approach was adopted for this study. Quantitative data were collected via a series of linked questionnaires; qualitative data were collected using focus group discussions, interviews and contemporaneous field notes. Analysis was undertaken using SPSS software and a phenomenological approach respectively.Findings: Participants indicated an increase in confidence in their ability to undertake dental procedures, which led to an increase in confidence in communication skills, and their ability to undertake complex restorative procedures. This led to greater treatment acceptance by patients resulting in better ‘job satisfaction’.Discussion: A sense of confidence is central to personal development and on‐going study, leading to firstly, an improved capability to perform tasks (competence), secondly, confidence is a product of the relationship and trust of those people associated with the individual/professional and thirdly, the correct level of challenge is important to confidence.Conclusions: The issue of confidence has not been looked at in postgraduate dentistry but it is well recognised in medical education fields.

Objective: To compare the acceptability and perceived helpfulness of an e-Oral Health intervention in form of text messages versus standard dental leaflets provided after a dental visit to patients aged 65 years and over.Background: Oral health care needs for older people are increasing. Remote interventions using e-Health can ensure oral care is provided despite physical hindrances or situations where dental appointments are limited such as has happened more widely during the COVID-19 pandemic.Materials and methods: Mixed-method nested study within a pilot trial. Dental patients (n = 150) at an outreach primary dental care centre, ≥ 65 years old, were recruited and randomly allocated to e-Oral health text messages or leaflet intervention arms. Post-intervention (6 months), participants responded to open and closed-ended two-way survey phone texts. Survey questions investigated: (a) whether they would recommend the intervention, (b) intervention helpfulness and (c) OPEN feedback. Average helpfulness scores (Scale:1= Very Helpful to 5= Not Helpful at All) were compared for each arm using Independent Sample t-test. Percentage of participants providing positive recommendations in each arm were compared using chi-squared tests. Qualitative findings were analysed using thematic analysis.Results: N = 68 (45%) responded. Mean helpfulness scores in text group M = 2.2, SD=1.1) and leaflet group M = 2.3, SD=1.9, P = .29. Amongst the text arm respondents, 89% compared with 68.2% in leaflet arm; P = .005 would recommend the intervention. Four qualitative themes were outlined: intervention approach, content, behavioural impact and recommendations.Conclusion: e-Oral Health text interventions are acceptable and helpful to older people, but these messages need to be tailored.

Objectives: Animal studies support a role for the gut microbiota in hypertension development, but large human studies are lacking. Here, we investigated the relationship between hypertension prevalence and gut microbial composition in two cohorts. Methods: We included 871 unrelated TwinsUK women with faecal microbiome data (16s rRNA gene sequencing). Multivariable linear models adjusted for age, age2 and BMI as well as MiRKAT models, were used to estimate the association of hypertension with alpha- and beta-diversity metrics. To identify taxa associated with hypertension, a generalized additive model for location scale and shape was computed adjusting for covariates and multiple testing. Results were replicated in 448 women from PREDICT-1. Results: We found that measures of alpha diversity are significantly lower in hypertensive cases [Beta(95% confidence interval, 95% CI) = −0.05 (−0.095 to −0.004), P = 0.03] and a significant association between beta diversity and hypertension (FDR

Coxiella burnetii is the causative agent of Q fever. It can manifest in both acute and chronic forms. Culture-negative endocarditis is the most common and serious presenting form of chronic Q fever. This occurs almost exclusively in patients with a pre-existing valvulopathy including valve prosthesis or immunocompromised patients as well as in pregnant women. Diagnosis is often delayed or missed due to the nonspecific symptoms of the condition. Without the proper antimicrobial therapy, the mortality is high. Q fever endocarditis should be suspected especially in people who recently had acute Q fever, people who come from endemic areas as well as people with occupational contact with sheep, goats and cattle and endocarditis symptoms. In this article we present a case with a patient who died of unknown cause and where PCR performed on autopsy of the valve revealed Q fever endocarditis.

Background The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. Methods In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI

Background Chronic inflammation, which can be modulated by diet, is linked to high white blood cell counts and correlates with higher cardiometabolic risk and risk of more severe infections, as in the case of COVID-19. Methods Here, we assessed the association between white blood cell profile (lymphocytes, basophils, eosinophils, neutrophils, monocytes and total white blood cells) as markers of chronic inflammation, habitual diet and gut microbiome composition (determined by sequencing of the 16S RNA) in 986 healthy individuals from the PREDICT-1 nutritional intervention study. We then investigated whether the gut microbiome mediates part of the benefits of vegetable intake on lymphocyte counts. Results Higher levels of white blood cells, lymphocytes and basophils were all significantly correlated with lower habitual intake of vegetables, with vegetable intake explaining between 3.59 and 6.58% of variation in white blood cells after adjusting for covariates and multiple testing using false discovery rate (q Collinsella, known to increase with the intake of processed foods and previously associated with fatty liver disease. We further correlated white blood cells to other inflammatory markers including IL6 and GlycA, fasting and post-prandial glucose levels and found a significant relationship between inflammation and diet. Conclusion A habitual diet high in vegetables, but not fruits, is linked to a lower inflammatory profile for white blood cells, and a fifth of the effect is mediated by the genus Collinsella. Trial registration The ClinicalTrials.gov registration identifier is NCT03479866.

Background Academic reading and writing are seen as self-evident literacy competences in most contemporary higher educations, however, whether students also are introduced to professional literacy of relevance for dentistry during their education is a question. The purpose of this study is to analyze one of the Swedish dental programmes, with respect to its design, in relation to possible content of relevance for academic and professional literacy. Secondarily, to identify and analyze Swedish dental students’ writing in an academic setting, i.e. what these students are expected to read and write, and how they write. Methods Data, for this ethnographically inspired case-study, was produced by observations and audio-recordings of lectures, copies of teachers’ handouts and of volunteering students’ notes, and a multiple-choice-test. Data-analysis was made in five steps, starting with macro-level data, i.e. curriculum and syllabuses, followed by the syllabuses for the two observed modules, the teacher-provided material, analysis of the students’ notes, while in the fifth and final step, the results from the previous steps were compared, to find patterns of what students were expected to read and write, and what in the teacher-provided multimodal material that was emphasized in teachers’ talk. Results This study showed that students were engaged in several types of literacy events, such as reading, finding and watching videos on their learning platform, writing, and following instructions. The study also showed that there is a recurrent academic content comprised of anatomy, physiology and pathology, while the professional content comprised of patient communication and anamnesis. Further, an integrated content was found and was initiated in teacher-constructed PowerPoints and by student-questions. Note-taking patterns varied between individual students, but the general pattern for this group of students were the use of complementary notes. This type of note-taking was used to make available further descriptions of the teacher-constructed text in PowerPoints, but also an independent text describing pictures shown on teachers’ PowerPoints or the blackboard. Conclusion Findings from the present study reveal that students either copy text from teachers’ PowerPoint-slides, re-formulate text from teachers’ PowerPoint-slides, or write complementing text to teachers’ PowerPoint-slides. Further, the students individually choses type of note-taking based on situation. The study also revealed that the academic literacy – in the two modules during the fifth and sixth semesters of a dental education analyzed – mainly has a professional basis for reading, writing, and communication purposes. The study also showed that academic and professional literacy are closely connected through recurrent integration.

Personalised dietary modulation of the gut microbiota may be key to disease management. Current investigations provide a broad understanding of the impact of diet on the composition and activity of the gut microbiota, yet detailed knowledge in applying diet as an actionable tool remains limited. Further to the relative novelty of the field, approaches are yet to be standardised and extremely heterogeneous research outcomes have ensued. This may be related to confounders associated with complexities in capturing an accurate representation of both diet and the gut microbiota. This review discusses the intricacies and current methodologies of diet-microbial relations, the implications and limitations of these investigative approaches, and future considerations that may assist in accelerating applications. New investigations should consider improved collection of dietary data, further characterisation of mechanistic interactions, and an increased focus on -omic technologies such as metabolomics to describe the bacterial and metabolic activity of food degradation, together with its crosstalk with the host. Furthermore, clinical evidence with health outcomes is required before therapeutic dietary strategies for microbial amelioration can be made. The potential to reach detailed understanding of diet-microbiota relations may depend on re-evaluation, progression, and unification of research methodologies, which consider the complexities of these interactions.

Background The transition from upper secondary to higher education and from higher education to professional practice requires that students adapt to new literacy practices, academic and professional. However, there is a gap of knowledge regarding literacy practices in dental education. Therefore, the aim of this study was to identify what characterizes dental students’ notetaking and secondarily to determine what dental students express regarding their notetaking. Methods To analyze students’ perspectives about the purposes of notetaking and to examine their written notes in depth, three volunteer students, out of the 24 students that voluntarily and anonymously handed in their notes, were interviewed. The three undergraduate dental students that participated in this material-based, semi-structured interview study, framed within a New Literacy Studies approach, were on their third year (6th semester). The focus of these material-based interviews was on each student’s notes. Questions prepared for semi-structured interviews were open-ended and allowed for individual follow-up questions related to the interviewee’s answer. To analyze the outcome of the interviews a thematic analysis was used. Results From the material-based interviews eight themes that relate to what, how and for what purpose students write were discerned. These eight themes include professional vocabulary, core content as well as clinical examples that belong to what students read and write; multimodal accentuation as well as synthesis that belong to how students read and write; and mnemonic strategies, academic purposes, and professional purposes that belong to for what purpose students read and write. Conclusions Findings from the interviews indicate that the digital development, offering a variety of available tools, has expanded the notion of notetaking. This study identified that dental students’ notetaking has changed during their education from initially being synchronous, to also include multimodal and asynchronous writing, making notetaking more of a writing practice. Further, students’ writing practices seem to be motivated by their knowledge formation in relation to a subject matter, but also in relation to their experiences during clinical training. Although, our hypothesis was that the main purpose of notetaking and writing was to pass their course examinations, this study showed that students that were half-way through their dental education, are aware that literacy practices are for learning for their future profession, and not only for passing their exams.

Extracellular matrix (ECM)-related adhesion proteins are important in metastasis. Ras suppressor-1 (RSU-1), a suppressor of Ras-transformation, is localized to cell&ndash, ECM adhesions where it interacts with the Particularly Interesting New Cysteine-Histidine rich protein (PINCH-1), being connected to Integrin Linked Kinase (ILK) and alpha-parvin (PARVA), a direct actin-binding protein. RSU-1 was also found upregulated in metastatic breast cancer (BC) samples and was recently demonstrated to have metastasis-promoting properties. In the present study, we transiently silenced RSU-1 in BC cells, MCF-7 and MDA-MB-231. We found that RSU-1 silencing leads to downregulation of Growth Differentiation Factor-15 (GDF-15), which has been associated with both actin cytoskeleton reorganization and metastasis. RSU-1 silencing also reduced the mRNA expression of PINCH-1 and cell division control protein-42 (Cdc42), while increasing that of ILK and Rac regardless of the presence of GDF-15. However, the downregulation of actin-modulating genes PARVA, RhoA, Rho associated kinase-1 (ROCK-1), and Fascin-1 following RSU-1 depletion was completely reversed by GDF-15 treatment in both cell lines. Moreover, complete rescue of the inhibitory effect of RSU-1 silencing on cell invasion was achieved by GDF-15 treatment, which also correlated with matrix metalloproteinase-2 expression. Finally, using a graph clustering approach, we corroborated our findings. This is the first study providing evidence of a functional association between RSU-1 and GDF-15 with regard to cancer cell invasion.

In many solid tumours a desmoplastic reaction takes place, which results in tumour tissue stiffening due to the extensive production of extracellular matrix (ECM) proteins, such as collagen, by stromal cells, mainly fibroblasts (FBs) and cancer-associated fibroblasts (CAFs). In this study, we investigated the effect of collagen stiffness on pancreatic FBs and CAFs, particularly on specific cytoskeleton properties and gene expression involved in tumour invasion. We found that cells become stiffer when they are cultured on stiff substrates and express higher levels of alpha-smooth muscle actin (α-SMA). Also, it was confirmed that on stiff substrates, CAFs are softer than FBs, while on soft substrates they have comparable Young's moduli. Furthermore, the number of spread FBs and CAFs was higher in stiffer substrates, which was also confirmed by Ras-related C3 botulinum toxin substrate 1 ( RAC1 ) mRNA expression, which mediates cell spreading. Although stress fibres in FBs become more oriented on stiff substrates, CAFs have oriented stress fibres regardless of substrate stiffness. Subsequently, we demonstrated that cells' invasion has a differential response to stiffness, which was associated with regulation of Ras homologue family member ( RhoA ) and Rho-associated, coiled-coil containing protein kinase 1 ( ROCK-1 ) mRNA expression. Overall, our results demonstrate that collagen stiffness modulates FBs and CAFs cytoskeleton remodelling and alters their invasion properties.

The aim of this study was to investigate if intramuscular injection of sterile water can be used as a human experimental pain model that resembles clinical craniofacial muscle pain and to analyse if the effects differ between sexes.This randomised, double-blind, placebo-controlled cross-over study included 30 healthy age-matched women and men (23.6 ± 2.4 years). At three sessions, with at least one week of washout in between, 0.2 mL of either sterile water (test-substance), hypertonic saline (58.5 mg/mL; active control) or isotonic saline (0.9 mg/mL; passive control) was randomly injected into the right masseter muscle. Pain intensity (VAS) was continuously assessed during 5 min whereafter pain duration (s) and pain area (au) were calculated; pressure pain thresholds (PPT;kPa) were recorded every 5 minutes during 30 minutes.Sterile water evoked pain of similar intensity (74.5 ± 49.9) as hypertonic saline (74.0 ± 50.5); whereas, isotonic saline evoked low-intensity pain (11.4 ± 23.4). The pain induced by sterile water and hypertonic saline had higher intensity (P 0.001), longer duration (P 0.001) and larger pain area (P 0.001) than isotonic saline. There were no significant differences in any pain variable between sterile water and hypertonic saline. The PPT did not change significantly after any substance, except for in women 5 minutes after sterile water injection (P 0.002). Pain duration was longer in the men for all substances (P 0.006), while the pain area was larger in women after injection of hypertonic saline (P 0.003).These results indicate that pain evoked by sterile water resembles clinical muscle pain and may offer a novel and simpler alternative to hypertonic saline injections.

Nutrition plays a key role in blood pressure (BP) regulation. Here, we examine associations between nutrient intakes and BP in a large predominantly female population-based cohort. We assessed the correlation between 45 nutrients (from food frequency questionnaires) and systolic BP/diastolic BP (SBP/DBP) in 3889 individuals from TwinsUK not on hypertensive treatments and replicated in an independent subset of monozygotic twins discordant for nutrient intake (17&ndash, 242 pairs). Results from both analyses were meta-analysed. For significant nutrients, we calculated heritability using structural equation modelling. We identified and replicated 15 nutrients associated with SBP, 9 also being associated with DBP, adjusting for covariates and multiple testing. 14 of those had a heritable component (h2: 27.1&ndash, 57.6%). Strong associations with SBP were observed for riboflavin (Beta(SE) = &minus, 1.49(0.38),P = 1.00 &times, 10&minus, 4) and tryptophan (&minus, 0.31(0.01),P = 5 &times, 4), while with DBP for alcohol (0.05(0.07),P = 1.00 &times, 4) and lactose (&minus, 0.05(0.0),P = 1.3 &times, 3). Two multivariable nutrient scores, combining independently SBP/DBP-associated nutrients, explained 22% of the variance in SBP and 13.6% of the variance in DBP. Moreover, bivariate heritability analysis suggested that nutrients and BP share some genetic influences. We confirm current understanding and extend the panel of dietary nutrients implicated in BP regulation underscoring the value of nutrient focused dietary research in preventing and managing hypertension.

Cancer is a multifactorial disease responsible for millions of deaths worldwide. It has a strong genetic background, as mutations in oncogenes or tumor suppressor genes contribute to the initiation of cancer development. Integrin signaling as well as the signaling pathway of Ras oncogene, have been long implicated both in carcinogenesis and disease progression. Moreover, they have been involved in the promotion of metastasis, which accounts for the majority of cancer-related deaths. Ras Suppressor-1 (RSU1) was identified as a suppressor of Ras-induced transformation and was shown to localize to cell-extracellular matrix adhesions. Recent findings indicate that its expression is elevated in various cancer types, while its role in regulating metastasis-related cellular processes remains largely unknown. Interestingly, there is no in vivo work in the field to date, and thus, all relevant knowledge stems from in vitro studies. In this review, we summarize recent studies using breast, liver and brain cancer cell lines and highlight the role of RSU1 in regulating cancer cell invasion.

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor and it is associated with poor survival. Integrin-linked kinase (ILK) is a serine/threonine protein pseudo-kinase that binds to the cytoplasmic domains of β1 and β3 integrins and has been previously shown to promote invasion and metastasis in many cancer types, including GBM. However, little is known regarding the exact molecular mechanism implicating ILK in GBM aggressiveness. In this study, we used two brain cell lines, the non-invasive neuroglioma H4 cells, and the highly invasive glioblastoma A172 cells, which express ILK in much higher levels than H4. We studied the effect of ILK silencing on the metastatic behavior of glioblastoma cells in vitro and elucidate the underlying molecular mechanism. We showed that siRNA-mediated silencing of ILK inhibits cell migration and invasion of the highly invasive A172 cells while it does not affect the migratory and invasive capacity of H4 cells. These data were also supported by respective changes in the expression of Rho-associated kinase 1 (ROCK1), fascin actin-bundling protein 1 (FSCN1), and matrix metalloproteinase 13 (MMP13), which are known to regulate cell migration and invasion. Our findings were further corroborated by analyzing the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) dataset. We conclude that ILK promotes glioblastoma cell invasion through activation of ROCK1 and FSCN1 in vitro, providing a more exact molecular mechanism for its action. This work was funded by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC Grant Agreement No. 336839-ReEngineeringCancer (to TS).

As metastasis accounts for most breast cancer (BC)-related deaths, identifying key players becomes research priority. Growth differentiation factor-15 (GDF15), a member of the transforming growth factor-β superfamily, is affected by the actin cytoskeleton and has been associated with cancer. However, its exact role in BC cell invasiveness is vague. GDF15 short-hairpin (shRNA)-mediated silencing was used to inhibit GDF15 expression in MCF-7 and MDA-MB-231 BC cells and gene expression of relevant focal adhesion (FA) genes, cell migration, invasion and tumor spheroid invasion were subsequently analyzed. GDF15 silencing promoted cell migration, cell invasion as well as tumor spheroid invasion and up-regulated urokinase plasminogen activator (uPA) and FA genes, integrin-linked kinase (ILK), LIM zinc finger domain containing 1 (LIMS1), α-parvin (PARVA), and RAS suppressor-1 (RSU1). Computational analysis of Cancer Genome Atlas BC dataset however, revealed no significant correlation between GDF15 expression and metastasis pointing towards a more complex molecular interplay between GDF15, actin cytoskeleton and FA-related genes which ultimately affects their expression pattern, in vivo. GDF15 suppresses BC cell invasion in vitro through down-regulation of FA genes but its role in BC is more complicated in vivo and warrants further investigation. The study was funded by the European Research Council, European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336839-ReEngineeringCancer.

A multi-residue method for the simultaneous analysis of a wide range of pesticides in raisins using liquid and gas chromatography-tandem mass spectrometry (LC-MS/MS and GC–MS/MS) has been validated. Pesticides are extracted from raisins with ethyl acetate, followed by centrifugation. The validation study was in accordance with DG SANTE guidelines. Validation experiments have been performed in both analytical instruments. A total number of 314 pesticides were spiked in raisins of organic farming at two spiking levels for GC–MS/MS (0.025 and 0.1 mg/kg), and at three spiking levels for LC-MS/MS (0.005, 0.05, and 0.1 mg/kg) with 6 replicates at each concentration. The scope of validation included linearity, limits of quantification (LOQ), accuracy, precision, and matrix effects (%) for each pesticide. The validated method was then applied for the analysis of 37 commercial raisin samples purchased from the market. For the evaluation of the results, processing factors (PFs) have been applied to derive the amount of residue in raisins, from the maximum residue levels (MRLs) of grapes, and which in this paper will be referred as to the MRL expressed in raisins. In all conventional samples, pesticides were detected at concentrations above the LOQ. In total, 55 different pesticides were detected. All conventional samples contained multiple pesticides ranging from 2 to 24. On the other hand, samples from organic farming were found to be free of the analysed pesticides. The 13.5% of the examined samples were considered as violations. The exposure assessment for the acute risk of the violating samples indicated that no potential risk derives from the detected and approved in the EU pesticides, while the detection of not approved pesticides in the EU, and the lack of toxicological reference values for certain pesticides raise concerns for the human health, especially for children. The results of the survey study indicate the need to include processed samples, and in particular dry fruits with a high consumption rate such as raisins, in the official controls of pesticide residues in food.

Intracerebral hemorrhage (ICH) is a deadly and debilitating type of stroke, caused by the rupture of cerebral blood vessels. To date, there are no restorative interventions approved for use in ICH patients, highlighting a critical unmet need. ICH shares some pathological features with other acute brain injuries such as ischemic stroke (IS) and traumatic brain injury (TBI), including the loss of brain tissue, disruption of the blood-brain barrier, and activation of a potent inflammatory response. New biomaterials such as hydrogels have been recently investigated for their therapeutic benefit in both experimental IS and TBI, owing to their provision of architectural support for damaged brain tissue and ability to deliver cellular and molecular therapies. Conversely, research on the use of hydrogels for ICH therapy is still in its infancy, with very few published reports investigating their therapeutic potential. Here, the published use of hydrogels in experimental ICH is commented upon and how approaches reported in the IS and TBI fields may be applied to ICH research to inform the design of future therapies is described. Unique aspects of ICH that are distinct from IS and TBI that should be considered when translating biomaterial-based therapies between disease models are also highlighted.

This study investigated if repeated buffered acidic saline infusions into the masseter muscles induced muscle pain and mechanical sensitization. Fourteen healthy men participated in this double-blind, randomized, and placebo-controlled study. Two repeated infusions (day 1 and 3) were given in the masseter muscles with either a buffered acidic saline solution (pH 5.2) or an isotonic saline solution (pH 6) as control. After 10 days of wash-out, the experiment was repeated with the other substance. Pressure pain thresholds (PPT), pain intensity, maximum unassisted mouth opening (MUO), and pain drawings were assessed before, directly following, and after each infusion at 5, 15, and 30 min and on day 4 and 7. Fatigue and pain intensity were assessed after a one-minute chewing test 30 min after infusions and day 4 and 7. Acidic saline induced higher pain intensity than control day 3 up to 5 min after infusions, but did not affect PPT. The chewing test did not evoke higher fatigue during chewing or MUO or after acidic saline infusion compared to control. Repeated acidic saline infusions in the masseter muscles induced a short-lasting muscle pain without mechanical hyperalgesia or functional pain. Hence, this model might not be superior to already existing experimental muscle pain models.

Background Both temporomandibular disorders myalgia (TMDM) and fibromyalgia (FM) have been linked to central and peripheral changes in serotonin availability. The precursor of serotonin, tryptophan (TRP), is mainly catabolised via another pathway to produce kynurenine (KYN), but whether changes of this pathway are present in TMDM and FM are still unclear. Objective The aim was to explore blood plasma concentrations of TRP and KYN in TMDM and FM in an attempt to identify novel associations for future research. Methods Plasma of 113 female participants (17 TMDM, 40 FM and 56 healthy pain-free controls) were analysed for TRP and KYN concentrations. The degradation of TRP via the KYN pathway was indicated by the KYN to TRP ratio (KYN/TRP). Pain intensities were assessed with the Graded Chronic Pain Scale (GCPS) and Visual Analogue Scale (VAS). Psychological symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS), Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder scale (GAD-7). Results In TMDM there was a negative correlation between TRP and pain intensity (rs = -0.55 P = .023) and positive correlations between KYN/TRP and pain intensity (rs = 0.59 P = .013). In FM, KYN/TRP was negatively correlated with anxiety symptoms (rs = -0.36 P = .022) and a trend towards significantly lower TRP levels was found compared to controls (P = .05). Conclusion The association between KYN/TRP and pain intensity as well as anxiety ratings in this small exploratory study may indicate that KYN/TRP could be a relevant indicator for symptom severity in TMDM and FM. Further investigations of the KYN pathway in chronic myalgia are warranted.