A Computational Study of Dynamic Obstruction in Type B Aortic Dissection.

A serious complication in aortic dissection is dynamic obstruction of the true lumen (TL). Dynamic obstruction results in malperfusion, a blockage of blood flow to a vital organ. Clinical data reveal that increases in central blood pressure promote dynamic obstruction. However, the mechanisms by which high pressures result in TL collapse are underexplored and poorly understood. Here, we developed a computational model to investigate biomechanical and hemodynamical factors involved in Dynamic obstruction. We hypothesize that relatively small pressure gradient between TL and false lumen (FL) are sufficient to displace the flap and induce obstruction. An idealized fluid-structure interaction model of type B aortic dissection was created. Simulations were performed under mean cardiac output while inducing dynamic changes in blood pressure by altering FL outflow resistance. As FL resistance increased, central aortic pressure increased from 95.7 to 115.3 mmHg. Concurrent with blood pressure increase, flap motion was observed, resulting in TL collapse, consistent with clinical findings. The maximum pressure gradient between TL and FL over the course of the dynamic obstruction was 4.5 mmHg, consistent with our hypothesis. Furthermore, the final stage of dynamic obstruction was very sudden in nature, occurring over a short time (<1 s) in our simulation, consistent with the clinical understanding of this dramatic event. Simulations also revealed sudden drops in flow and pressure in the TL in response to the flap motion, consistent with first stages of malperfusion. To our knowledge, this study represents the first computational analysis of potential mechanisms driving dynamic obstruction in aortic dissection.

Clostridium difficile infection and risk of Parkinson's disease: a Swedish population-based cohort study.

BACKGROUND AND PURPOSE: Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). The aim of this study was to examine whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD. METHODS: We performed a population-based cohort study using Swedish national register data. Adults aged ≥35 years were identified from the Swedish Population and Housing Census 1990 and followed during the period 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs. outpatient), presence of recurrent infections, and pre-infection use of antibiotics. RESULTS: Amongst the study population (N = 4 670 423), 34 868 (0.75%) had a history of CDI. A total of 165 and 47 035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among the CDI group [hazard ratio 1.16, 95% confidence interval (CI)1.00-1.36], which was mainly driven by increased PD risk within the first 2 years after CDI diagnosis (hazard ratio 1.38, 95% CI 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups. CONCLUSIONS: Clostridium difficile may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.

Physical exercise and non-insulin glucose-lowering therapies in the management of Type 2 diabetes mellitus: a clinical review.

In the UK the National Institute of Health and Care Excellence (NICE) advocates intensive lifestyle programmes that attain the levels of daily physical activity set out by the Chief Medical Officer as a first-line strategy for improving the health of people at risk of developing diabetes or reducing the risk of development of Type 2 diabetes. For people with Type 2 diabetes, lifestyle measures complement pharmacological treatments that include both oral and injectable therapies. In line with this, NICE guidelines also support intensification of efforts to improve patient lifestyle along with these glucose-lowering therapies. There is a paucity of evidence, however, in the available published literature examining the association between glucose-lowering therapies and exercise metabolism. In the present review we explore the current knowledge with regard to the potential interactions of oral and non-insulin injectable therapies with physical activity in people at risk of, or who have, Type 2 diabetes, and present evidence that may inform healthcare professionals of the need to monitor patients more closely in their adaptation to both pharmacological therapy and physical activity.

Oral health needs assessment world-wide in relation to HIV. Themes: Oral health needs and inequalities, oral health promotion, co-ordinating research and enhancing dissemination in relation to HIV- a workshop report.

OBJECTIVES: Review the meaning of 'health need', consider oral health inequalities and oral health promotion among people with HIV and outline methods to enhance coordination, standardization and dissemination of research efforts. METHODS: This workshop involved a brief introduction of each topic by an invited speaker followed by participant discussion. Participants were dentists and dental students attending the 7th World Workshop on Oral Health & Disease in AIDS RESULTS: A health need was regarded as a population's ability to benefit from care. Oral health inequalities called for both downstream and upstream health promotion. A community health programme to reach people with HIV infection in the community was described. Despite deploying community health workers to reduce costs, the programme required additional resources for comprehensive implementation. The Indian National AIDS Control Program exemplified coordinated efforts. Knowledge transfer can be achieved via educational, linkage and exchange and organizational interventions. Stakeholder engagement in a combination of all three types of intervention is the most effective. CONCLUSIONS: The discussion centred on the difficulties of Indian dentists who felt they did not receive sufficient revenue to treat patients with HIV. An opposing view approach treated all patients using universal standards of infection control. Dental regulatory bodies, professional organizations and governments may need to demonstrate leadership and advocacy for the oral health of people with HIV infection.

Reducing Inequalities in Oral Health in the Africa and Middle East Region.

Dentistry is facing many serious challenges and threats. Addressing them will require major changes in strategy. This work outlines the extent of dental disease in the Africa and Middle East Region (AMER) and suggests strategies to reduce inequalities in oral health. The main oral health challenges in the AMER relate to controlling the relentless increase in caries with age. A very conservative estimate of population caries levels suggests that a 5-fold increase in dental personnel would be required just to treat current levels of caries. Hence, we argue that current approaches to control caries in the AMER are both ineffective and unaffordable, and a new model to promote oral health is needed. Unless determinants of noncommunicable diseases are addressed and access to evidence-based minimal intervention dental care is improved, the burden of dental disease will persist. The new oral health promotion model calls for an integrated intersectoral common risk factor approach, namely, "oral health in all policies" (OHiAP). An OHiAP framework will initiate high-level policy initiatives and intersectoral partnerships. Oral health professionals have an important advocacy role in securing the fundamental changes in health strategy needed to control the growing, unjust, and unaffordable burden of oral disease.

MDCT findings of aortic branch artery pseudoaneurysms associated with type B intramural haematoma.

PURPOSE: The purpose of this study was to evaluate prevalence, morphological characteristics and evolution of aortic branch artery pseudoaneurysms associated with type B aortic intramural haematoma (IMH) using multidetector computed tomography (MDCT). MATERIALS AND METHODS: We enrolled 14 patients (nine men; mean age 64.6±9.6; range 42-75 years) with a diagnosis in the acute phase of type B IMH without evidence of intimal tear. All patients underwent clinical and MDCT follow-up. RESULTS: Twenty-two pseudoaneurysms in six patients (6/14, 43%) were observed at MDCT. In the majority of patients (5/6, 83%) the pseudoaneurysms were multiple and involved the branches of the descending thoracic aorta (14/22, 64%), mainly the intercostal arteries (11/22, 50%). At a mean follow-up of 10.6±8.7 months, 21 pseudoaneurysms showed resolution, reduction or dimensional stability (95%), whereas only one increased in size (5%). CONCLUSIONS: Aortic branch artery pseudoaneurysms associated with IMH may be considered a benign disease, as the majority of cases resolved or did not change in size, with haematoma resorption. However, because a dynamic change in pseudoaneurysms in the acute and subacute phases was frequently observed, close clinical and imaging follow-up is mandatory.

The GI Simulated Clinic in the Era of COVID-19: a Comparison of Virtual to In-Person Delivery.

The COVID-19 pandemic has significantly impacted medical education; thus, there is a need to better understand the effectiveness of virtual learning compared to in-person learning. This is a single-center, cross-sectional study of first-year medical students who attended a gastroenterology simulated clinic activity in person in 2018 and 2019 or virtually in 2020. Participants were surveyed on the activity's relevance and effectiveness. Students' assessment of the virtual clinic's effectiveness and relevance was not significantly different from the in-person version of the activity. In addition, most students rated the virtual clinic as effective for learning about telemedicine.

An International Working Definition for Quality of Oral Healthcare.

To assess and improve the quality of oral healthcare, we must first agree on what constitutes good care. Currently there is no internationally accepted definition for quality of oral healthcare. Therefore, the purpose of the study was to establish a working definition for quality of oral healthcare that would help to advance further improvements in the field of quality improvement in oral healthcare. The development of the working definition included a 3-step approach: 1) literature screening; 2) expert-based compilation of an initial list of topics, leaning on the National Academy of Medicine framework for quality of care; and 3) a World Café with voting, which took place during the annual general meeting of the International Association for Dental Research in 2018. Following this approach, the collective intelligence of involved participants yielded a comprehensive list of items, prioritized by relevance. The resulting working definition comprises 7 domains­patient safety, effectiveness, efficiency, patient-centeredness, equitability, timeliness, access to care­and 30 items, which together characterize quality of oral healthcare. This aspirational working definition provides the potential to facilitate further conversations and activities aiming at quality improvement in oral healthcare. KNOWLEDGE TRANSFER STATEMENT: This special communication describes the development of a working definition for quality of oral healthcare. The findings of this study are intended to raise awareness of the relevance of quality improvement initiatives in oral healthcare. The working definition described here has the potential to facilitate further conversations and activities aiming at quality improvement in oral healthcare.

Mediastinal masses masquerading as common respiratory conditions of childhood: a case series.

INTRODUCTION: Leukaemia and lymphoma may present with symptoms and signs mimicking common respiratory conditions of childhood such as asthma or croup. The UK National Institute for Clinical Excellence guidelines for referral for suspected cancer state that "the primary healthcare professional should be ready to review the initial diagnosis in patients in whom common symptoms do not resolve as expected" and "must be alert to the possibility of cancer when confronted by unusual symptom patterns" (National Institute for Health and Clinical Excellence, 2005). RESULTS AND DISCUSSION: A child with an undiagnosed mediastinal mass presenting with signs and symptoms suggestive of asthma or croup may be given oral systemic steroids. We report four such illustrative cases presenting to a single institution within the last 3 years. CONCLUSION: We highlight key points from the history and examination findings which should lead to review of the original diagnosis, the benefit of early chest X-ray in such cases and the dangers of steroid pretreatment.

Initiating and maintaining resistance training in older adults: a social cognitive theory-based approach.

Numerous research studies performed in "lab-gyms" with supervised training have demonstrated that simple, brief (20-30 min) resistance training protocols performed 2-3/week following the American College of Sports Medicine's guidelines positively affect risk factors associated with heart disease, cancers, diabetes, sarcopenia and other disabilities. For more than a decade, resistance training has been recommended for adults, particularly older adults, as a prime preventive intervention, and increasing the prevalence of resistance training is an objective of Healthy People 2010. However, the prevalence rate for resistance training is only estimated at 10-15% for older adults, despite the leisure time of older adults and access to facilities in developed countries. The reasons that the prevalence rate remains low include public health policy not emphasising resistance training, misinformation, and the lack of theoretically driven approaches demonstrating effective transfer and maintenance of training to minimally supervised settings once initial, generally successful, supervised training is completed. Social cognitive theory (SCT) has been applied to physical activity and aerobic training with some success, but there are aspects of resistance training that are unique including its intensity, progression, precision, and time and place specificity. Social cognitive theory, particularly with a focus on self-regulation and response expectancy and affect within an ecological context, can be directly applied to these unique aspects of resistance training for long-term maintenance.

What, exactly, is cladistics? Re-writing the history of systematics and biogeography.

The development of comparative biology (systematics) has been of interest to philosophers and historians. Particular attention has been placed on the 'war' of the 1970s and 1980s, the apparent dispute among those who preferred this or that methodology. In this contribution we examine the history of comparative biology from the perspective of fundamentals rather than methodologies. Our examination is framed within the artificial-natural classification dichotomy, a viewpoint currently lost from view but worth resurrecting.

Kinase chips hit the proteomics era.

Protein kinase chips, in which kinases are tested for their ability to phosphorylate immobilized substrates, have been developed and used to evaluate the protein kinases encoded by the yeast genome. This new technology promises to be a valuable addition to the biochemists' and cell biologists' arsenal for evaluating the substrate selectivity and function of protein kinases in cell signaling.

The role of superoxide anion radical in the reduction of ferritin iron by xanthine oxidase.

Superoxide dismutase exerted a pronounced inhibitory effect upon xanthine oxidase-mediated reduction of iron in ferritin, ferric chloride, or ferric ADP. Maximal inhibition was observed when the superoxide dismutase concentration was only about 1% of that found in normal porcine liver. These observations indicate that superoxide anion radical is an intermediate in the reduction of iron by xanthine oxidase in vitro but not in vivo.

Enhancing the catalytic repertoire of nucleic acids: a systematic study of linker length and rigidity.

The incorporation of potentially catalytic groups in DNA is of interest for the in vitro selection of novel deoxyribozymes. A series of 10 C5-modified analogues of 2'-deoxyuridine triphosphate have been synthesised that possess side chains of differing flexibility and bearing a primary amino or imidazole functionality. For each series of nucleotide analogues differing degrees of flexibility of the C5 side chain was achieved through the use of alkynyl, alkenyl and alkyl moieties. The imidazole function was conjugated to these C5-amino-modified nucleotides using either imidazole 4-acetic acid or imidazole 4-acrylic acid (urocanic acid). The substrate properties of the nucleotides (fully replacing dTTP) with TAQ polymerase during PCR have been investigated in order to evaluate their potential applications for in vitro selection experiments. 5-(3-Aminopropynyl)dUTP and 5-(E-3-aminopropenyl)dUTP and their imidazole 4-acetic acid- and urocanic acid-modified conjugates were found to be substrates. In contrast, C5-amino-modified dUTPs with alkane or Z-alkene linkers and their corresponding conjugates were not substrates. The incorporation of these analogues during PCR has been confirmed by inhibition of restriction enzyme digestion using XBAI and by mass spectrometry of the PCR products.

Enhancing the catalytic repertoire of nucleic acids. II. Simultaneous incorporation of amino and imidazolyl functionalities by two modified triphosphates during PCR.

The incorporation of potentially catalytic groups into DNA is of interest for the in vitro selection of novel deoxyribozymes. We have devised synthetic routes to a series of three C7 modified 7-deaza-dATP derivatives with pendant aminopropyl, Z-aminopropenyl and aminopropynyl side chains. These modified triphosphates have been tested as substrates for Taq polymerase during PCR. All the modifications are tolerated by this enzyme, with the aminopropynyl side chain giving the best result. Most protein enzymes have more than one type of catalytic group located in their active site. By using C5-imidazolyl-modified dUTPs together with 3-(aminopropynyl)-7-deaza-dATP in place of the natural nucleotides dTTP and dATP, we have demonstrated the simultaneous incorporation of both amino and imidazolyl moieties into a DNA molecule during PCR. The PCR product containing the four natural bases was fully digested by XbaI, while PCR products containing the modified 7-deaza-dATP analogues were not cleaved. Direct evidence for the simultaneous incorporation during PCR of an imidazole-modified dUTP and an amino-modified 7-deaza-dATP has been obtained using mass spectrometry.

Attitudes to fluorosis and dental caries by a response latency method.

BACKGROUND: Understanding socially relevant attitudes to fluorosis and dental caries is important. Previous studies have concentrated mainly on aesthetic implications. AIMS: To investigate social judgements beyond the aesthetic, made when viewing digitally manipulated extraoral images of dental fluorosis of varying degrees of severity and images of dental caries. METHODOLOGY: Using a response latency technique, which allowed both the direction and strength of attitudes to be measured, 40 volunteers made judgements on 144 image/characteristic combinations. RESULTS: Participants made social judgements which extended beyond the aesthetic to factors such as sociability, reliability and cleanliness. Judgements on mild fluorosis were not markedly different from those made about the same individual with normal enamel, but severe fluorosis had a significant negative impact on social judgements. Untreated dental caries was judged less favourably than normal enamel and mild fluorosis. CONCLUSIONS: Attribution of characteristics that go beyond the aesthetic are significantly influenced by altered tooth appearance.