An Osteoconductive, Osteoinductive, and Osteogenic Tissue-Engineered Product for Trauma and Orthopaedic Surgery: How Far Are We?

The management of large bone defects due to trauma, degenerative disease, congenital deformities, and tumor resection remains a complex issue for the orthopaedic reconstructive surgeons. The requirement is for an ideal bone replacement which is osteoconductive, osteoinductive, and osteogenic. Autologous bone grafts are still considered the gold standard for reconstruction of bone defects, but donor site morbidity and size limitations are major concern. The use of bioartificial bone tissues may help to overcome these problems. The reconstruction of large volume defects remains a challenge despite the success of reconstruction of small-to-moderate-sized bone defects using engineered bone tissues. The aim of this paper is to understand the principles of tissue engineering of bone and its clinical applications in reconstructive surgery

Activities forgone because of chronic breathlessness: a cross-sectional, population prevalence study

BackgroundChronic breathlessness is a prevalent, disabling syndrome affecting many people for years. Identifying the impact of chronic breathlessness on people’s activities in the general population is pivotal for designing symptom management strategies. ObjectiveThis study aimed to evaluate the association between chronic breathlessness and activities respondents identify can no longer be undertaken (‘activities foregone’). DesignThis population-based, cross sectional, online survey used a market research company’s database of 30,000 registrants for each sex, generating the planned sample size - 3,000 adults reflecting Australia’s 2016 Census by sex, age group, state of residence and rurality. Setting/Subjects The population of focus (n=583) reported a modified Medical Research Council (mMRC) breathlessness scale >1 and experienced this breathlessness for >3 months. MeasurementsActivities forgone were categorised by mMRC using coding derived from the Dyspnea Management Questionnaire domains. Activities were classified as ‘higher/lower intensity’ using Human Energy Expenditure scale.ResultsRespondents were: male 50.3%; median age 50.0 (IQR 29.0); with 66% living in metropolitan areas; reporting 1,749 activities forgone. For people with mMRC 1 (n=533), 35% had not given up any activity, decreasing to 9% for mMRC 2 (n=38) and 3% for mMRC 3-4 (n=12). Intense sport (e.g. jogging, bike riding) was the top activity forgone: 42% (mMRC 1); 32% (mMRC 2); and 36% (mMRC 3-4). For respondents with mMRC 3-4, the next most prevalent activities foregone were ‘sexual activities’ (14%); ‘lower intensity sports’ (11%) and ‘other activities’ (11%).ConclusionsPeople progressively reduce a wide range of activities because of their chronic breathlessness

A new classification of cardio-oncology syndromes

Abstract Increasing evidence suggests a multifaceted relationship exists between cancer and cardiovascular disease (CVD). Here, we introduce a 5-tier classification system to categorize cardio-oncology syndromes (COS) that represent the aspects of the relationship between cancer and CVD. COS Type I is characterized by mechanisms whereby the abrupt onset or progression of cancer can lead to cardiovascular dysfunction. COS Type II includes the mechanisms by which cancer therapies can result in acute or chronic CVD. COS Type III is characterized by the pro-oncogenic environment created by the release of cardiokines and high oxidative stress in patients with cardiovascular dysfunction. COS Type IV is comprised of CVD therapies and diagnostic procedures which have been associated with promoting or unmasking cancer. COS Type V is characterized by factors causing systemic and genetic predisposition to both CVD and cancer. The development of this framework may allow for an increased facilitation of cancer care while optimizing cardiovascular health through focused treatment targeting the COS type

Single Crystal Functional Oxides on Silicon

Single crystalline thin films of complex oxides show a rich variety of functional properties such as ferroelectricity, piezoelectricity, ferro and antiferromagnetism etc. that have the potential for completely new electronic applications (1-2). Direct synthesis of such oxides on Si remains challenging due to the fundamental crystal chemistry and mechanical incompatibility of dissimilar interfaces (3-16). Here we report integration of thin (down to 1 unit cell) single crystalline, complex oxide films onto Si substrates, by epitaxial transfer at room temperature. In a field effect transistor using a transferred Pb0.2Zr0.8TiO3 (PZT) layer as the gate insulator, we demonstrate direct reversible control of the semiconductor channel charge with polarization state. These results represent the realization of long pursued but yet to be demonstrated single crystal functional oxides on-demand on silicon

Coffee Somatic Embryogenesis: How Did Research, Experience Gained and Innovations Promote the Commercial Propagation of Elite Clones From the Two Cultivated Species?

Since the 1990s, somatic embryogenesis (SE) has enabled the propagation of selected varieties, Arabica F1 hybrid and Robusta clones, originating from the two cultivated coffee species, Coffea arabica and Coffea canephora, respectively. This paper shows how mostly empirical research has led to successful industrial transfers launched in the 2000s in Latin America, Africa, and Asia. Coffee SE can be considered as a model for other woody perennial crops for the following reasons: (i) a high biological efficiency has been demonstrated for propagated varieties at all developmental stages, and (ii) somaclonal variation is understood and mastered thanks to intensive research combining molecular markers and field observations. Coffee SE is also a useful model given the strong economic constraints that are specific to this species. In brief, SE faced four difficulties: (i) the high cost of SE derived plants compared to the cost of seedlings of conventional varieties, (ii) the logistic problems involved in reaching small-scale coffee growers, (iii) the need for certification, and (iv) the lack of solvency among small-scale producers. Nursery activities were professionalized by introducing varietal certification, quality control with regard to horticultural problems and somaclonal variation, and sanitary control for Xylella fastidiosa. In addition, different technology transfers were made to ensure worldwide dissemination of improved F1 Arabica hybrids and Robusta clones. Innovations have been decisive for successful scaling-up and reduction of production costs, such as the development of temporary immersion bioreactors for the mass production of pre-germinated embryos, their direct sowing on horticultural soil, and the propagation of rejuvenated SE plants by rooted mini-cuttings. Today, SE is a powerful tool that is widely used in coffee for biotechnological applications including propagation and genetic transformation. Basic research has recently started taking advantage of optimized SE protocols. Based on -omics methodologies, research aims to decipher the molecular events involved in the key developmental switches of coffee SE. In parallel, a high-throughput screening of active molecules on SE appears to be a promising tool to speed-up the optimization of SE protocols

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context

Background: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. Aims: The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. Method: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. Results: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. Conclusion: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk

Influence of fluid ingestion on heart rate, cardiac autonomic modulation and blood pressure in response to physical exercise : a systematic review with meta-analysis and meta-regression

A systematic review was undertaken to investigate the involvement of hydration in heart rate (HR), HR variability (HRV) and diastolic (DBP) and systolic (SBP) blood pressure in response to exercise. Data synthesis: The EMBASE, MEDLINE, Cochrane Library, CINAHL, LILACS and Web of Science databases were searched. In total, 977 studies were recognized, but only 36 were included after final screening (33 studies in meta-analysis). This study includes randomized controlled trials (RCTs) and non-RCTs with subjects > 18 years old. The hydration group consumed water or isotonic drinks, while the control group did not ingest liquids. For the hydration protocol (before, during and after exercise), the HR values during the exercise were lower compared to the controls (−6.20 bpm, 95%CI: −8.69; −3.71). In the subgroup analysis, “water ingested before and during exercise” showed lower increases in HR during exercise (−6.20, 95%CI: 11.70 to −0.71), as did “water was ingested only during exercise” (−6.12, 95%CI: −9.35 to −2.89). Water intake during exercise only revealed a trend of avoiding greater increases in HR during exercise (−4,60, 95%CI: −9.41 to 0.22), although these values were not significantly different (p = 0.06) from those of the control. “Isotonic intake during exercise” showed lower HRs than the control (−7.23 bpm, 95% CI: −11.68 to −2.79). The HRV values following the exercise were higher in the hydration protocol (SMD = 0.48, 95%CI: 0.30 to 0.67). The values of the SBP were higher than those of the controls (2.25 mmHg, 95%CI: 0.08 to 4.42). Conclusions: Hydration-attenuated exercise-induced increases in HR during exercise, improved autonomic recovery via the acceleration of cardiac vagal modulation in response to exercise and caused a modest increase in SBP values, but did not exert effects on DBP following exercise

Characterization of DNA with an 8-oxoguanine modification

The oxidation of DNA resulting from reactive oxygen species generated during aerobic respiration is a major cause of genetic damage that, if not repaired, can lead to mutations and potentially an increase in the incidence of cancer and aging. A major oxidation product generated in cells is 8-oxoguanine (oxoG), which is removed from the nucleotide pool by the enzymatic hydrolysis of 8-oxo-2′-deoxyguanosine triphosphate and from genomic DNA by 8-oxoguanine-DNA glycosylase. Finding and repairing oxoG in the midst of a large excess of unmodified DNA requires a combination of rapid scanning of the DNA for the lesion followed by specific excision of the damaged base. The repair of oxoG involves flipping the lesion out of the DNA stack and into the active site of the 8-oxoguanine-DNA glycosylase. This would suggest that thermodynamic stability, in terms of the rate for local denaturation, could play a role in lesion recognition. While prior X-ray crystal and NMR structures show that DNA with oxoG lesions appears virtually identical to the corresponding unmodified duplex, thermodynamic studies indicate that oxoG has a destabilizing influence. Our studies show that oxoG destabilizes DNA (ΔΔG of 2–8 kcal mol−1 over a 16–116 mM NaCl range) due to a significant reduction in the enthalpy term. The presence of oxoG has a profound effect on the level and nature of DNA hydration indicating that the environment around an oxoG•C is fundamentally different than that found at G•C. The temperature-dependent imino proton NMR spectrum of oxoG modified DNA confirms the destabilization of the oxoG•C pairing and those base pairs that are 5′ of the lesion. The instability of the oxoG modification is attributed to changes in the hydrophilicity of the base and its impact on major groove cation binding