Relationships among Cortisol, Perceived Stress, and Dental Caries Experience in Adolescents and Young Adults.

INTRODUCTION: Stress can impact mental and physical health, especially during adolescence and young adulthood, but the extent of its contribution to dental caries is poorly understood. The present study assessed the association between perceived stress, cortisol levels (in hair and saliva), and overall caries experience of adolescents and young adults aged 15-25 years. METHODS: Hair and saliva samples were obtained from 93 participants free of periodontal disease. Cortisol in hair and saliva was determined using a competitive enzyme-linked immunosorbent assay. Participants completed a perceived stress questionnaire and underwent full-mouth oral examination by a calibrated examiner. Dental caries experience was based on the decayed, missing, and filled teeth (DMFT) index. Sociodemographic variables were also recorded. RESULTS: There were significantly higher hair cortisol levels and perceived stress scale (PSS) scores in individuals with dental caries experience (DMFT≥1) than in those without (DMFT = 0). However, there was no significant difference in salivary cortisol concentration. A binary logistic regression revealed that higher hair cortisol levels and greater scores on the perceived stress scale were associated with increased odds of having experienced dental caries. In contrast, no significant association was found between salivary cortisol concentration and dental caries. Using multivariable regression models, caries experience was found to be significantly associated with both hair cortisol levels and PSS scores. These associations remained statistically significant even after adjusting for sociodemographic variables. CONCLUSION: Hair cortisol levels and perceived stress have a significant association with dental caries experience, whereas salivary cortisol concentrations do not.

Exploring the experiences of people with urogynaecology conditions in the UK: a reflexive thematic analysis and conceptual model.

BACKGROUND: Urogynaecological conditions, such as pelvic organ prolapse, urinary incontinence, and urinary tract infection, can have a profound impact on people's lives. The Independent Medicines and Medical Devices Safety Review highlights missed opportunities to prevent harm when patient voices are not incorporated into healthcare policy and practice. This resonates with the Women's Health Strategy for England. The National Institute for Health and Care Research (NIHR) Policy Research Programme funded this in-depth qualitative exploration of people's experiences of living with urogynaecological conditions, and of seeking healthcare treatment, to inform health and social care improvements in the UK. METHODS: We conducted in-depth interviews online or by telephone (April 2021-December 2021) and used reflexive thematic analysis to develop themes that cut across urogynaecological conditions. RESULTS: We spoke to seventy-four adults aged 22-84 across a range of backgrounds and lived experiences of urogynaecological conditions, including pelvic organ prolapse, urinary incontinence and persistent or recurring urinary tract infection. Eight themes were developed: [1] I get no respite from my own body; [2] I feel confined and separated; [3] I can no longer be 'me'; [4] I am constrained by stigma, shame and silence; [5] I feel fragmented and lost in the healthcare system; [6] I need to be heard, believed, and valued; [7] I need respect as an equal partner in healthcare; and [8] (Re)connected to a more open community. CONCLUSIONS: High quality care focuses on the whole person rather than their body parts. Openness and candour support a shared decision-making model of care. A culture of shame can have a negative impact on access to health care and recovery.

Stakeholder Engagement in the Development of Public Health Economic Models: An Application to Modelling of Minimum Unit Pricing of Alcohol in South Africa.

BACKGROUND: Health economic models aim to provide decision makers with information that is contextually relevant, understandable and credible. This requires ongoing engagement throughout the research project between the modeller and end-users. OBJECTIVES: We aim to reflect on how a public health economic model of minimum unit pricing of alcohol in South Africa benefited from, and was shaped by, stakeholders. We outline how engagement activities were used during the development, validation and communication phases of the research with input gathered at each stage to inform future priorities. METHODS: A stakeholder mapping exercise was completed to identify stakeholders with the required knowledge, for example academics with expertise in modelling alcohol harm in South Africa, members of civil society organisations with lived experience of informal alcohol outlets, and policy professionals working at the forefront of alcohol policy development in South Africa. The stakeholder engagement consisted of four phases: developing a detailed understanding of the local policy context; co-producing model focus and structure; scrutinising model development and communication planning; and communicating research evidence to end-users. The first phase utilised 12 individual semi-structured interviews. Phases two to four centred around face-to-face workshops (two online) with both individual and group-based exercises employed to achieve required outputs. RESULTS: Phase one provided key learning on policy context and initiated working relationships. Phases two to four provided a conceptualisation of the problem of alcohol harm in South Africa and the choice of policy to model. Stakeholders chose population subgroups of interest and advised on both economic and health outcomes. They provided input on critical assumptions, data sources, priorities for future work, and communication strategies. The final workshop provided a platform to communicate the results of the model to a largely policy audience. These activities led to the production of highly contextualised research methods and findings that were able to be communicated widely beyond academia. CONCLUSIONS: Our programme of stakeholder engagement was fully integrated into the research programme. It resulted in a number of benefits including creating positive working relationships, guiding modelling decisions, tailoring the research to the context, and providing ongoing opportunities for communication.

Titanium Alloy Implants with Lattice Structures for Mandibular Reconstruction.

In recent years, the field of mandibular reconstruction has made great strides in terms of hardware innovations and their clinical applications. There has been considerable interest in using computer-aided design, finite element modelling, and additive manufacturing techniques to build patient-specific surgical implants. Moreover, lattice implants can mimic mandibular bone's mechanical and structural properties. This article reviews current approaches for mandibular reconstruction, their applications, and their drawbacks. Then, we discuss the potential of mandibular devices with lattice structures, their development and applications, and the challenges for their use in clinical settings.

Neighborhood-Level Inequalities in Dental Care of Adolescents and Young Adults in Southwestern Ontario.

We examined whether the association of neighborhood-level socioeconomic status (SES) with the cost of dental care and dental care outcomes differs between adolescents and young adults. A total of 2915 patient records were split into two groups: adolescents (15 to 17 years of age) and young adults (18 to 24 years of age). Three dental care outcomes-routine oral evaluation (OEV-CH-A), utilization of preventive services (PRV-CH-A), and dental treatment services (TRT-CH-A)-were determined according to the Dental Quality Alliance (DQA) criteria. Associations of neighborhood SES and other sociodemographic variables with dental care outcomes and the cost of dental care were assessed using binary logistic and univariate linear regression models, respectively. Young adults had significantly lower PRV-CH-A and higher TRT-CH-A scores when compared to adolescents. We observed a significant negative association between TRT-CH-A and median household income in both adolescents and young adults. Utilization of dental treatment services was positively associated with the cost of care in both age groups, whereas utilization of preventive services was inversely associated with the cost of care in young adults, but not in adolescents. Neighborhood-level income was inversely associated with increased TRT-CH-A in both young adults and adolescents. In summary, young adults showed significantly worse preventive and treatment outcomes when compared to adolescents. Moreover, individuals from neighborhoods with a lower household income showed a significantly higher cost of dental care, yet worse treatment outcomes.

Combating the Current Pandemic and Preparing for the Next: Lessons Learned From the COVID-19 Pandemic From the Perspective of Deployed Special Operations Forces.

The coronavirus 2019 (COVID-19) pandemic continues to be a threat to global health, including the health of deployed armed forces. Servicemembers had to adjust to the "new normal" while maintaining the interests of the nation's security as well as that of our host nation partners. This commentary examines how Special Operations Forces operating within four different regions worldwide leveraged the challenges presented by the onset of this pandemic in maintaining stability, sustaining a ready force, and operating forward deployed. Deployed forces face constant difficulties with logistical support, varied medical resources access and a medical system predominantly focused on trauma care. At the onset of the COVID-19 pandemic there was little guidance specific to these circumstances which required an improvised adaptation of the recommendations set by national and Department of Defense medical authorities. Plans were constantly revised to match the ever changing medical and operational environment. Strategies such as the "Bubble Philosophy" and tiered force protection measures helped our units to maintain a rigorous training cycle. New methods of communication and training with our host nation partners such as the use of Unmanned Aerial Systems (UAS) platforms to survey host nation training became standard. Through these measures all of our forces were able to maintain operational capacity, protect the force, and maintain rapport with the host nations. We hope these experiences will provide a rough framework for future forces faced with a similar struggle. We also want to stress that challenges vary depending on the area of operations and the pathogen responsible for the pandemic. Any feedback and collaboration that may come from this work is appreciated and encouraged.

Luciferase-based GloSensor™ cAMP assay: Temperature optimization and application to cell-based kinetic studies.

G protein-coupled receptors (GPCRs) are an important receptor superfamily and common therapeutic targets. The second messenger cyclic adenosine monophosphate (cAMP) is a key mediator in many GPCR signaling pathways. Monitoring intracellular cAMP levels can help identify orthosteric agonists and antagonists, as well as allosteric modulators. In this regard, luminescence-based biosensors have revolutionized our ability to monitor GPCR signaling kinetics. The GloSensor™ cAMP assay enables real-time monitoring of signaling downstream of many GPCRs. However, it is crucial to optimize assay conditions such as temperature. As well, it has not been reported whether the effects of temperature on biosensor activity are reversible. Here, we describe the temperature sensitivity and reversibility of the GloSensor™ cAMP assay, and which GloSensor™ version is optimal for measuring cytosolic cAMP. We also present a detailed protocol for monitoring cAMP levels in live cells expressing endogenous or exogenous GPCRs. Temperature optimization studies were carried out using HEK293H cells transiently transfected with the adenosine receptor A2a and the GloSensor™ plasmid (pGloSensor-20F or -22F). We found that preincubation and luminescence reading at room temperature were optimal as compared to higher temperatures. As well, the GloSensor-22F biosensor had a superior signal-to-background ratio and the effect of temperature on biosensor activity was reversible. However, thermal instability of the biosensor may pose a problem for in vivo studies. Nevertheless, the GloSensor™ cAMP assay can be applied to analyze signaling by a wide range of GPCRs for drug discovery purposes.

Clinician perspectives on having point of care tests made available to them during out of hours home visiting.

BACKGROUND: Little is known about clinicians' perspectives on the use of point of care (POC) tests in assessment of acute illness during primary care out of hours (OOH) care. During a service improvement project, POC tests (including creatinine, electrolytes, haemoglobin and lactate) were made available to clinicians undertaking OOH home visits, with the clinicians allowed absolute discretion about when and whether they used them. METHOD: To explore clinicians' perspectives on having POC tests available during OOH home visits, we undertook a qualitative study with clinicians working in Oxfordshire OOH home visiting teams. We conducted 19 Semi-structured interviews with clinicians working in OOH, including those who had and had not used the POC tests available to them. To explore evolving perspectives over time, including experience and exposure to POC tests, we offered clinicians the opportunity to be interviewed twice throughout the study period. Our sample included 7 GPs (4 interviewed once, 3 interviewed twice - earlier and later during the study), 6 emergency practitioners (EPs) including advanced nurse practitioners and paramedics, 1 Healthcare Assistant, and 2 ambulatory care physicians. Interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: The clinicians reflected on their decision-making to use (or not use) POC tests, including considering which clinical scenarios were "appropriate" and balancing the resources and time taken to do POC tests against what were perceived as likely benefits. The challenges of using the equipment in patients' homes was a potential barrier, though could become easier with familiarity and experience. Clinicians who had used POC tests described benefits, including planning onward care trajectories, and facilitating communication, both between professionals and with patients and their families. CONCLUSION: Clinicians described a discriminatory approach to using POC tests, considering carefully in which situations they were likely to add value to clinical decision-making.

Female Urgency, Trial of Urodynamics as Routine Evaluation (FUTURE study): a superiority randomised clinical trial to evaluate the effectiveness and cost-effectiveness of invasive urodynamic investigations in management of women with refractory overactive bladder symptoms.

BACKGROUND: Overactive bladder (OAB) syndrome is a symptom complex affecting 12-14% of the UK adult female population. Symptoms include urinary urgency, with or without urgency incontinence, increased daytime urinary frequency and nocturia. OAB has a negative impact on women's social, physical, and psychological wellbeing. Initial treatment includes lifestyle modifications, bladder retraining, pelvic floor exercises and pharmacological therapy. However, these measures are unsuccessful in 25-40% of women (refractory OAB). Before considering invasive treatments, such as Botulinum toxin injection or sacral neuromodulation, most guidelines recommend urodynamics to confirm diagnosis of detrusor overactivity (DO). However, urodynamics may fail to show evidence of DO in up to 45% of cases, hence the need to evaluate its effectiveness and cost-effectiveness. FUTURE (Female Urgency, Trial of Urodynamics as Routine Evaluation) aims to test the hypothesis that, in women with refractory OAB, urodynamics and comprehensive clinical assessment is associated with superior patient-reported outcomes following treatment and is more cost-effective, compared to comprehensive clinical assessment only. METHODS: FUTURE is a pragmatic, multi-centre, superiority randomised controlled trial. Women aged ≥ 18 years with refractory OAB or urgency predominant mixed urinary incontinence, and who have failed/not tolerated conservative and medical treatment, are considered for trial entry. We aim to recruit 1096 women from approximately 60 secondary/tertiary care hospitals across the UK. All consenting women will complete questionnaires at baseline, 3 months, 6 months and 15 months post-randomisation. The primary outcome is participant-reported success at 15 months post-randomisation measured using the Patient Global Impression of Improvement. The primary economic outcome is incremental cost per quality-adjusted life year gained at 15 months. The secondary outcomes include adverse events, impact on other urinary symptoms and health-related quality of life. Qualitative interviews with participants and clinicians and a health economic evaluation will also be conducted. The statistical analysis of the primary outcome will be by intention-to-treat. Results will be presented as estimates and 95% CIs. DISCUSSION: The FUTURE study will inform patients, clinicians and policy makers whether routine urodynamics improves treatment outcomes in women with refractory OAB and whether it is cost-effective. TRIAL REGISTRATION: ISRCTN63268739 . Registered on 14 September 2017.

Ectopic mineralisation of the mandibular symphysis in ENT1 knockout mice: A model of dystrophic calcification.

Equilibrative nucleoside transporter 1 (ENT1) transfers nucleosides, such as adenosine, across plasma membranes. We reported previously that mice lacking ENT1 (ENT1 -/- ) exhibit progressive ectopic calcification of spinal tissues-a phenotype resembling diffuse idiopathic skeletal hyperostosis (DISH) in humans. Our objective was to investigate potential calcification of orofacial tissues in ENT1 -/- mice. Heads of wild-type mice and ENT1 -/- mice from 3 to 17 months were evaluated using microcomputed tomography (µCT). Some heads were decalcified and processed for histological assessment. Other heads were examined using energy dispersive X-ray spectroscopy and micro X-ray diffraction. Using µCT, ENT1 -/- mice showed extensive radiopaque lesions within the mandibular symphysis, the severity of which increased with advancing age. Histologically, at 6 months these ectopic radiopacities were found to correspond to acellular, amorphous, eosinophilic material, with no evidence of inflammatory cells. Because lesions were localised to the symphysis, we identified early pathological changes at 3 months and observed that lesions initiated specifically within the fibrocartilage pad. Energy-dispersive X-ray spectroscopy of ectopic lesions revealed large amounts of calcium and phosphorous in a molar ratio of ~1.59, and X-ray diffraction profiles matched that of calcium-deficient hydroxyapatite. This is the first characterisation of ectopic calcifications within the mandibular symphysis of ENT1 -/- mice, indicating a role for ENT1 and adenosine metabolism in regulating calcification of fibrocartilaginous tissues. Moreover, these murine lesions resemble areas of dystrophic calcification in the spinal tissues of humans with DISH. Importantly, ectopic calcifications develop in a reproducible temporal pattern within a well-defined anatomical region and, thus, provide a model for determining the cellular and molecular pathways underlying ectopic calcification in DISH and related disorders.

Overriding water table control on managed peatland greenhouse gas emissions.

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

Value of cervical electrical impedance spectroscopy to predict spontaneous preterm delivery in asymptomatic women: the ECCLIPPx prospective cohort study.

OBJECTIVES: Preterm birth (PTB) accounts for two-thirds of deaths of structurally normal babies and is associated with substantial lifetime healthcare costs. Prevention of PTB remains limited by the modest accuracy of prediction methods, namely transvaginal ultrasound (TVS) cervical length (CL) measurement and quantitative cervicovaginal fetal fibronectin (FFN) estimation. We report the first substantive study detailing the predictive performance of a cervical probe device based on electrical impedance spectroscopy (EIS) for PTB - the EleCtriCaL Impedance Prediction of Preterm birth by spectroscopy of the cervix (ECCLIPPx) study. We aimed to compare the accuracy of cervical EIS-based prediction of spontaneous PTB with that of prediction using TVS-CL and FFN in asymptomatic women in the mid-trimester. METHODS: We studied asymptomatic women with a singleton pregnancy at 20-22 weeks' and 26-28 weeks' gestation. EIS was performed using a Sheffield Mark 5.0 device that makes measurements in the frequency range 76 Hz to 625 kHz using a small probe housing tetrapolar electrodes. TVS-CL and FFN were also measured. The associations of cervical EIS, TVS-CL and FFN with spontaneous delivery before 37 weeks and before 32 weeks were determined by multivariate linear and non-linear logistic regression analysis. Areas under the receiver-operating-characteristics curves (AUC) plots of sensitivity against specificity were used to compare the predictive performance of all parameters, both in isolation and in combination. RESULTS: Of the 365 asymptomatic women studied at 20-22 weeks who were not receiving treatment, 29 had spontaneous PTB, 14 had indicated PTB and 322 had term birth. At the higher frequencies assessed, cervical EIS predicted spontaneous PTB before 37 weeks with an AUC of 0.76 (95% CI, 0.71-0.81), compared with AUCs of 0.72 (95% CI, 0.66-0.76) for TVS-CL and 0.62 (95% CI, 0.56-0.72) for FFN. Combining all three assessments improved the prediction of spontaneous PTB before 37 weeks (AUC, 0.79 (95% CI, 0.74-0.83)) compared with TVS-CL and FFN alone. Incorporating a history of spontaneous PTB (defined as previous mid-trimester miscarriage or spontaneous PTB (14 to < 37 weeks)) into the cervical EIS prediction model improved the accuracy of prediction of spontaneous PTB before 37 weeks (AUC, 0.83 (95% CI, 0.78-0.87)) and before 32 weeks (AUC, 0.86 (95% CI, 0.82-0.90)). CONCLUSIONS: Mid-trimester cervical EIS assessment predicts spontaneous PTB. Larger confirmatory studies investigating its potential clinical utility and to inform effective preventive interventions are required. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Factors associated with advanced colorectal cancer differ between young and older adults in England: a population-based cohort study.

AIM: Advanced stage presentation of colorectal cancer is associated with poorer survival outcomes, particularly among young adults. This study aimed to determine whether demographic risk factors for advanced stage presentation differed between young and older adults. METHOD: Individual-level data on all incident colorectal cancers in people aged 20 years and above were extracted from the National Cancer Registration and Analysis Service database for the years 2012 to 2015. Patients were divided into two cohorts: young-onset colorectal cancer (YOCC) if aged 20-49 years and older-onset colorectal cancer (OOCC) if aged 50 years and above. Logistic regression was used to identify risk factors for advanced stage presentation, defined as TNM Stage III or IV, in each cohort. RESULTS: There were 7075 (5.2%) patients in the YOCC cohort and 128 345 (94.8%) patients in the OOCC cohort. Tumours in the YOCC cohort were more likely to be at an advanced stage (67.2% vs 55.3%, P < 0.001) and located distally (63.7% vs 55.4%, P < 0.001). No demographic factor was consistently associated with advanced stage presentation in the YOCC cohort. Among the OOCC cohort, increased social deprivation [OR (Index of Multiple Deprivation quintile 5 vs 1) = 1.11 (95% CI 1.07-1.16), P < 0.001], Black/Black British ethnicity [OR (baseline White) = 1.25 (95% CI 1.11-1.40), P < 0.001] and residence in the East Midlands [OR (baseline London) = 1.11 (95% CI 1.04-1.17), P = 0.001] were associated with advanced stage presentation. CONCLUSION: Demographic factors associated with advanced disease were influenced by age. The effects of social deprivation and ethnicity were only observed in older adults and mirror trends in screening uptake. Targeted interventions for high-risk groups are warranted.

Osteoclasts and their circulating precursors in rheumatoid arthritis: Relationships with disease activity and bone erosions.

Patients with rheumatoid arthritis (RA) have very different outcomes, particularly with regard to bone erosions. Since osteoclasts are responsible for bone destruction adjacent to rheumatoid synovium, profiling osteoclasts from circulating precursors in RA could help identify patients at risk for bone destruction. In this study, we sought to determine whether the functional characteristics of osteoclasts generated from their blood precursors were modified by RA activity or were intrinsic to osteoclasts and associated with the RA phenotype (erosive or not). Osteoclasts were generated in vitro from peripheral blood mononuclear cells (PBMCs) of subjects with RA (n = 140), as well as sex- and age-matched healthy controls (n = 101). Osteoclastic parameters were analyzed at baseline and during the follow-up for up to 4 years, with regular assessment of RA activity, bone erosions, and bone mineral density (BMD). As a validation cohort, we examined RA patients from the Early Undifferentiated PolyArthritis (EUPA) study (n = 163). The proportion of CD14+ PBMC was higher in RA than in control subjects, but inversely correlated with the 28-joint disease activity score (DAS28). Also surprisingly, in osteoclast cultures from PBMCs, active RA was associated with lower osteoclastogenic capacity, while in vitro bone resorption per osteoclast and resistance to apoptosis were similar in both active and quiescent RA. In a small subgroup analysis, osteoclasts from subjects with recent RA that had progressed at four years to an erosive RA exhibited at baseline greater resistance to apoptosis than those from patients remaining non-erosive. Our findings establish that when RA is active, circulating monocytes have a reduced potential to generate osteoclasts from PBMCs in vitro. In addition, osteoclasts associated with erosive disease had resistance to apoptosis from the start of RA.

Dystrophic calcification and heterotopic ossification in fibrocartilaginous tissues of the spine in diffuse idiopathic skeletal hyperostosis (DISH).

Diffuse idiopathic skeletal hyperostosis (DISH) is a prevalent noninflammatory spondyloarthropathy characterized by ectopic mineral formation along the anterolateral aspect of the vertebral column, yet little is known about its underlying pathogenesis. Our objective was to evaluate the histopathological features and composition of ectopic mineral within spinal tissues affected by DISH in humans. Thoracic spine segments from six embalmed cadaveric donors (one female and five males; median age 82 years) meeting the radiographic diagnostic criteria for DISH were evaluated using radiological, histological, and physical analyses. Overall, the histological features of ectopic mineralization at individual motion segments were heterogeneous, including regions of heterotopic ossification and dystrophic calcification. Heterotopic ossifications were characterized by woven and lamellar bone, multifocal areas of metaplastic cartilage, and bony bridges along the anterior aspect of the intervertebral disc space. Dystrophic calcifications were characterized by an amorphous appearance, a high content of calcium and phosphorus, an X-ray diffraction pattern matching that of hydroxyapatite, and radiodensities exceeding that of cortical bone. Dystrophic calcifications were found within the anterior longitudinal ligament and annulus fibrosus in motion segments both meeting and not meeting the radiographic criteria for DISH. In summary, our findings indicate that in DISH, ectopic mineral forms along the anterior aspect of the spine by both heterotopic ossification and dystrophic calcification of fibrocartilaginous tissues. Although both types of ectopic mineralization are captured by current radiographic criteria for DISH, dystrophic calcification may reflect a distinct disease process or an early stage in the pathogenesis of DISH.

Demographic trends in the incidence of young-onset colorectal cancer: a population-based study.

BACKGROUND: Evidence is emerging that the incidence of colorectal cancer is increasing in young adults, but the descriptive epidemiology required to better understand these trends is currently lacking. METHODS: A population-based cohort study was carried out including all adults aged 20-49 years diagnosed with colorectal cancer in England between 1974 and 2015. Data were extracted from the National Cancer Registration and Analysis Service database using ICD-9/10 codes for colorectal cancer. Temporal trends in age-specific incidence rates according to sex, anatomical subsite, index of multiple deprivation quintile and geographical region were analysed using Joinpoint regression. RESULTS: A total of 56 134 new diagnoses of colorectal cancer were analysed. The most sustained increase in incidence rate was in the group aged 20-29 years, which was mainly driven by a rise in distal tumours. The magnitude of incident rate increases was similar in both sexes and across Index of Multiple Deprivation quintiles, although the most pronounced increases in incidence occurred in the southern regions of England. CONCLUSION: Colorectal cancer should no longer be considered a disease of older people. Changes in incidence rates should be used to inform future screening policy, preventative strategies and research agendas, as well as increasing public understanding that younger people need to be aware of the symptoms of colorectal cancer.

ANTECEDENTES: Están apareciendo evidencias de que la incidencia del cáncer colorrectal (colorectal cancer, CRC) está aumentando en adultos jóvenes, pero se carece de la epidemiología descriptiva necesaria para comprender mejor estas tendencias. MÉTODOS: Se realizó un estudio de cohortes de base poblacional de todos los adultos de 20 a 49 años diagnosticados de CRC en Inglaterra entre 1974 y 2015. Los datos se extrajeron de la base de datos NCRAS utilizando los códigos ICD9/10 para el CRC. Las tendencias temporales en las tasas de incidencia específicas por edad (incidence rates, IR) según el sexo, la localización anatómica, el quintil del índice de privación múltiple (index of multiple deprivation, IMD) y la región geográfica se analizaron mediante un modelo de regresión joinpoint. RESULTADOS: Se analizaron un total de 56.134 nuevos diagnósticos de CRC. El aumento más sostenido en la IR se produjo en el grupo de edad de 20 a 29 años, principalmente a expensas de un incremento de los tumores distales. La magnitud de los aumentos de IR fue similar en ambos sexos y en los quintiles del IMD, aunque los aumentos más pronunciados en la incidencia se registraron en las regiones del sur de Inglaterra. CONCLUSIÓN: El CRC ya no debe ser considerado una enfermedad de las personas mayores: los cambios en las tasas de incidencia deberán tenerse en cuenta en las futuras políticas de cribado, en las estrategias preventivas y en los proyectos de investigación, así como para aumentar la toma de conciencia de la población de que las personas más jóvenes deben estar al corriente de los síntomas del CRC.

Vibration of osteoblastic cells using a novel motion-control platform does not acutely alter cytosolic calcium, but desensitizes subsequent responses to extracellular ATP.

Low-magnitude high-frequency mechanical vibration induces biological responses in many tissues. Like many cell types, osteoblasts respond rapidly to certain forms of mechanostimulation, such as fluid shear, with transient elevation in the concentration of cytosolic free calcium ([Ca2+ ]i ). However, it is not known whether vibration of osteoblastic cells also induces acute elevation in [Ca2+ ]i . To address this question, we built a platform for vibrating live cells that is compatible with microscopy and microspectrofluorometry, enabling us to observe immediate responses of cells to low-magnitude high-frequency vibrations. The horizontal vibration system was mounted on an inverted microscope, and its mechanical performance was evaluated using optical tracking and accelerometry. The platform was driven by a sinusoidal signal at 20-500 Hz, producing peak accelerations from 0.1 to 1 g. Accelerometer-derived displacements matched those observed optically within 10%. We then used this system to investigate the effect of acceleration on [Ca2+ ]i in rodent osteoblastic cells. Cells were loaded with fura-2, and [Ca2+ ]i was monitored using microspectrofluorometry and fluorescence ratio imaging. No acute changes in [Ca2+ ]i or cell morphology were detected in response to vibration over the range of frequencies and accelerations studied. However, vibration did attenuate Ca2+ transients generated subsequently by extracellular ATP, which activates P2 purinoceptors and has been implicated in mechanical signaling in bone. In summary, we developed and validated a motion-control system capable of precisely delivering vibrations to live cells during real-time microscopy. Vibration did not elicit acute elevation of [Ca2+ ]i , but did desensitize responses to later stimulation with ATP.

Altered forefoot function following a military training activity.

BACKGROUND: Injury rates are high in populations that regularly undertake weight-bearing physical activity, particularly military populations. Military training activities, that often include load carriage, have been associated with lower limb injury occurrence, specifically stress fractures. RESEARCH QUESTION: Recent work identified plantar loading variables as risk factors for lower limb stress fractures in Royal Marines recruits that were assessed during barefoot running. This study aimed to quantify how those plantar loading variables changed in Royal Marines recruits following a prolonged military load carriage activity, to further understand potential mechanisms for lower limb stress fractures. METHODS: Bilateral, synchronised plantar pressure and lower limb kinematic data were recorded during barefoot running at 3.6 m s-1 (±5%) pre- and post- a 12.8-km training activity (∼150 min). The training activity was completed with an average speed typical of walking (1.4 m.s-1), and 35.5 kg of additional load was carried throughout. Data were collected from 32 male Royal Marines recruits who completed the training activity in week-21 of the 32-week training programme. Plantar pressure variables and ankle dorsiflexion were compared between pre- and post-activity. RESULTS: Post-activity there was reduced loading under the forefoot and increased loading under the rearfoot and midfoot. There was no change in dorsiflexion touchdown angle, but an increase in peak dorsiflexion and range of motion post-activity. SIGNIFICANCE: The increased rearfoot loading, reduced forefoot loading and increased ankle dorsiflexion following a prolonged military load carriage activity suggest a reduced transfer of loading from the rearfoot to the forefoot during stance, which may have implications for the development of stress fractures, particularly of the metatarsals.

The effect of EMAT coil geometry on the Rayleigh wave frequency behaviour.

Understanding of optimal signal generation and frequency content for electromagnetic acoustic transducers (EMATs) is key to improving their design and signal to noise ratio. Linear and meander coil designs are fairly well understood, but other designs such as racetrack or focused coils have recently been proposed. Multiple transmission racetrack coil EMATs, with focused and unfocused designs, were constructed. The optimum driving frequency for maximum detected signal was found to range between 1.1 and 1.4 MHz on aluminium for a 1.5 mm width coil. A simple analytical model based on the instantaneous velocity of a wave predicts a maximum signal at 1.44 MHz. Modelling the detection coil as a spatial square wave agrees with this, and predicts a general relation of fP=0.761v/L between the optimum frequency fP, the wave velocity v, and the coil width L. A time domain model of the detection coil predicts a 1.4-1.5 MHz peak for continuous wave excitation, with a frequency that decreases as the length of the wavepacket is decreased, consistent with the experimental data. Linear coil modelling using the same technique is shown to be consistent with previous work, with improving detection at lower wave frequencies, and signal minima at every integer multiple of the wavelength. Finite Element Analysis (FEA) is used to model the effects of the spatial width of the racetrack generation coil and focused geometry, and no significant difference is found between the focused and the unfocused EMAT response. This highlights the importance of designing the EMAT coil for the correct lift-off and desired frequency of operation.