Ultrafast four-dimensional imaging of cardiac mechanical wave propagation with sparse optoacoustic sensing.

Propagation of electromechanical waves in excitable heart muscles follows complex spatiotemporal patterns holding the key to understanding life-threatening arrhythmias and other cardiac conditions. Accurate volumetric mapping of cardiac wave propagation is currently hampered by fast heart motion, particularly in small model organisms. Here we demonstrate that ultrafast four-dimensional imaging of cardiac mechanical wave propagation in entire beating murine heart can be accomplished by sparse optoacoustic sensing with high contrast, ∼115-µm spatial and submillisecond temporal resolution. We extract accurate dispersion and phase velocity maps of the cardiac waves and reveal vortex-like patterns associated with mechanical phase singularities that occur during arrhythmic events induced via burst ventricular electric stimulation. The newly introduced cardiac mapping approach is a bold step toward deciphering the complex mechanisms underlying cardiac arrhythmias and enabling precise therapeutic interventions.

Trust, Science Education and Vaccines.

The issue of trust in science has come to the fore in recent years. I focus on vaccines, first looking at what is known about trust in vaccines and then concentrating on whether what science education teaches about vaccines can be trusted. I present an argument to connect the phenomenon of vaccine hesitancy to the issue of trust and then argue for what an education about vaccines in school science might look like that takes seriously the notion of respect for students, including students who hold views about vaccination with which science teachers might disagree. Trust in others (people and institutions) varies greatly, both between countries and within countries, and depends on the characteristics of both trustor and trustee, and there are great differences in the extent to which people trust vaccines. However, it is a mistake to think that people who do not trust vaccines are simply ill-informed. There are a range of reasons for rejecting what is often an unexamined narrative about vaccines, namely that vaccines are always desirable. Many people come from communities that have sound reasons for being suspicious of what they are told by governments, business and the medical establishment. COVID-19 and earlier reactions to vaccination health scares show how important high-quality education about vaccines is. Much of that education can take place out of school, but the foundations are laid in school. Vaccine rejection and hesitancy have major global public health implications. Good quality vaccine education should help students understand about relevant biology and the nature of science; it should also be respectful of all students, including those who come from families that reject vaccines or are hesitant about them.

Hemodynamic response to sensory stimulation in mice: Comparison between functional ultrasound and optoacoustic imaging.

Intense efforts are underway to develop functional imaging modalities for capturing brain activity at the whole organ scale with high spatial and temporal resolution. Functional optoacoustic (fOA) imaging is emerging as a new tool to monitor multiple hemodynamic parameters across the mouse brain, but its sound validation against other neuroimaging modalities is often lacking. Here we investigate mouse brain responses to peripheral sensory stimulation using both fOA and functional ultrasound (fUS) imaging. The two modalities operate under similar spatio-temporal resolution regime, with a potential to provide synergistic and complementary hemodynamic readouts. Specific contralateral activation was observed with sub-millimeter spatial resolution with both methods. Sensitivity to hemodynamic activity was found to be on comparable levels, with the strongest responses obtained in the oxygenated hemoglobin channel of fOA. While the techniques attained highly correlated hemodynamic responses, the differential fOA readings of oxygenated and deoxygenated haemoglobin provided complementary information to the blood flow contrast of fUS. The multi-modal approach may thus emerge as a powerful tool providing new insights into brain function, complementing our current knowledge generated with well-established neuroimaging methods.

In vivo optoacoustic monitoring of percutaneous laser ablation of tumors in a murine breast cancer model.

Laser ablation (LA) is a promising approach for minimally invasive cancer treatments. Its in vivo applicability is often impeded by the lack of efficient monitoring tools that can help to minimize collateral tissue damage and aid in determining the optimal treatment end-points. We have devised a new, to the best of our knowledge, hybrid LA approach combining simultaneous volumetric optoacoustic (OA) imaging to monitor the lesion progression accurately in real time and 3D. Time-lapse imaging of laser ablation of solid tumors was performed in a murine breast cancer model in vivo by irradiation of subcutaneous tumors with a 100 mJ short-pulsed (${\sim}{5}\;{\rm ns}$∼5ns) laser operating at 1064 nm and 100 Hz pulse repetition frequency. Local changes in the OA signal intensity ascribed to structural alterations in the tumor vasculature were clearly observed, while the OA volumetric projections recorded in vivo appeared to correlate with cross sections of the excised tumors.

Ethical Challenges in Human Space Missions: A Space Refuge, Scientific Value, and Human Gene Editing for Space.

This article examines some selected ethical issues in human space missions including human missions to Mars, particularly the idea of a space refuge, the scientific value of space exploration, and the possibility of human gene editing for deep-space travel. Each of these issues may be used either to support or to criticize human space missions. We conclude that while these issues are complex and context-dependent, there appear to be no overwhelming obstacles such as cost effectiveness, threats to human life or protection of pristine space objects, to sending humans to space and to colonize space. The article argues for the rationality of the idea of a space refuge and the defensibility of the idea of human enhancement applied to future deep-space astronauts.

Science Education in the Light of COVID-19: The Contribution of History, Philosophy and Sociology of Science.

In this position paper, I examine how the history, philosophy and sociology of science (HPS) can contribute to science education in the era of the COVID-19 pandemic. I discuss shortcomings in the ways that history is often used in school science, and examine how knowledge of previous pandemics might help in teaching about COVID-19. I look at the potential of issues to do with measurement in the context of COVID-19 (e.g. measurement of mortality figures) to introduce school students to issues about philosophy of science, and I show how COVID-19 has the affordance to broaden and deepen the moral philosophy that students typically meet in biology lessons. COVID-19 also provides opportunities to introduce students to sociological ways of thinking, examining data and questioning human practices. It can also enable students to see how science, economics and politics inter-relate. In the final part of the paper, I suggest that there are strong arguments in favour of an interdisciplinary approach in tackling zoonoses like COVID-19 and that there is much to be said for such interdisciplinarity in school science lessons when teaching about socio-scientific issues and issues intended to raise scientific literacy.

Film Psychotherapy in the 21st Century.

Psychotherapy is commonly depicted in films. Films, then, help to inform the public about the nature of psychotherapy and psychotherapists. Although much has been written about the portrayal of psychotherapy in films, there has been little empirical investigation of films from the 21st century. The current study provides a systematic investigation of the portrayal of therapists and therapy in films released between 2000 and 2013. Trained volunteers coded films with characters identified as psychotherapists. Data are presented for ratings on 22 films in which therapist characters appeared on screen for at least 15 minutes. Therapists were predominantly Caucasian, male, and between ages 40 and 60 years. Their most common characteristics were generally positive-intelligent, caring, knowledgeable, and compassionate. More than half were portrayed as unethical, and more than one-third as manipulative. Therapists were also commonly shown as touching clients in some way, disclosing client information without permission, and becoming involved in social relationships with clients. In addition, it was often unclear whether clients benefitted from their engagement in therapy. The observed portrayals raise serious concerns about their potential impact on viewers. Viewers may be discouraged from seeking help and may have increased vulnerability to exploitation because of a lack of understanding of what is appropriate and inappropriate therapist behavior.

ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis.

Bone metastasis is mediated by complex interactions between tumor cells and resident stromal cells in the bone microenvironment. The functions of metalloproteinases in organ-specific metastasis remain poorly defined despite their well-appreciated role in matrix degradation and tumor invasion. Here, we show a mechanism whereby two distinct metalloproteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1) and matrix metalloproteinase-1 (MMP1), orchestrate a paracrine signaling cascade to modulate the bone microenvironment in favor of osteoclastogenesis and bone metastasis. Proteolytic release of membrane-bound epidermal growth factor (EGF)-like growth factors, including Amphiregulin (AREG), heparin-binding EGF (HB-EGF), and transforming growth factor alpha (TGFalpha) from tumor cells suppress the expression of osteoprotegerin (OPG) in osteoblasts and subsequently potentiate osteoclast differentiation. EGF receptor (EGFR) inhibitors block osteolytic bone metastasis by targeting EGFR signaling in bone stromal cells. Furthermore, elevated MMP1 and ADAMTS1 expression is associated with increased risk of bone metastasis in breast cancer patients. This study established MMP1 and ADAMTS1 in tumor cells, as well as EGFR signaling in osteoblasts, as promising therapeutic targets for inhibiting bone metastasis of breast cancer.

Hoarseness ­ causes and treatments. / Heiserkeit Ursachen und Therapie.

Due to a hoarseness or dysphonia about 1 % of patients consult a doctor. The causes of hoarseness are very diverse and can range from a harmless laryngitis to vocal cord tumors. In addition to acute and chronic laryngitis (42 % and 10 %), functional dysphonia (30 %), benign (15 %) and malignant tumors (3 %), vocal cord paresis (5 %), the physiological aging voice (2 %) and psychogenic factors (2 %) can cause hoarseness. The manifestation of internal diseases is very rare. Treatment options depending on the cause are drugs, voice therapy or surgery. The present article gives an overview of possible causes of hoarseness, diagnosis and treatment options. Hoarseness lasting more than three weeks should always be taken seriously and be examined laryngoscopically.

[Differential diagnostic and therapeutic aspects of nasal obstruction]. / Differenzialdiagnostische und therapeutische Aspekte.

A nasal obstruction can have various causes. This publication describes various diseases of the nose and paranasal sinuses which cause nasal obstruction or which are associated with the symptom of nasal obstruction. The diagnosis and treatment of the diseases is discussed. Anatomical, physiological aspects and the general diagnosis of diseases of the nose and sinuses are also considered.

Parenthood intentions of 16-18-year-olds in England: a survey of school students.

There is a need to understand teenagers' views towards having children to better tailor sexuality and reproductive health education. We conducted a survey of parenthood intentions for 16-18-year-old students. The survey was anonymous, contained open-ended and multiple-choice questions and was live from 10 May 2021 to 18 July 2022. The sample size was n = 931. Quantitative data were analysed descriptively and using chi-squared tests; qualitative data were analysed thematically. The majority of students (64%) indicated they wanted to have children in the future, with 49% desiring to have two children. Students who opted against having children cited the turbulent state of the world, concerns about parenthood, and, for many females, negative associations to pregnancy and childbirth. Many students felt concern about the possibility of having children in the future (45%), expressing concerns about their ability to have healthy children and worries about the lives their children might lead. Six themes were identified in their responses to the question 'What are your concerns about the possibility of having children in the future?': Fears; Self-doubt; Health and wellbeing; Big investment; Hinderance to personal aspirations; and Non-inclusive LGBTQ+ education. We conclude by making recommendations as to how school reproductive health and sex education might be improved.

Multi-Scale Volumetric Dynamic Optoacoustic and Laser Ultrasound (OPLUS) Imaging Enabled by Semi-Transparent Optical Guidance.

Major biological discoveries are made by interrogating living organisms with light. However, the limited penetration of un-scattered photons within biological tissues limits the depth range covered by optical methods. Deep-tissue imaging is achieved by combining light and ultrasound. Optoacoustic imaging exploits the optical generation of ultrasound to render high-resolution images at depths unattainable with optical microscopy. Recently, laser ultrasound has been suggested as a means of generating broadband acoustic waves for high-resolution pulse-echo ultrasound imaging. Herein, an approach is proposed to simultaneously interrogate biological tissues with light and ultrasound based on layer-by-layer coating of silica optical fibers with a controlled degree of transparency. The time separation between optoacoustic and ultrasound signals collected with a custom-made spherical array transducer is exploited for simultaneous 3D optoacoustic and laser ultrasound (OPLUS) imaging with a single laser pulse. OPLUS is shown to enable large-scale anatomical characterization of tissues along with functional multi-spectral imaging of chromophores and assessment of cardiac dynamics at ultrafast rates only limited by the pulse repetition frequency of the laser. The suggested approach provides a flexible and scalable means for developing a new generation of systems synergistically combining the powerful capabilities of optoacoustics and ultrasound imaging in biology and medicine.

Identification of function for CD44 intracytoplasmic domain (CD44-ICD): modulation of matrix metalloproteinase 9 (MMP-9) transcription via novel promoter response element.

CD44 is a multifunctional cell receptor that conveys a cancer phenotype, regulates macrophage inflammatory gene expression and vascular gene activation in proatherogenic environments, and is also a marker of many cancer stem cells. CD44 undergoes sequential proteolytic cleavages that produce an intracytoplasmic domain called CD44-ICD. However, the role of CD44-ICD in cell function is unknown. We take a major step toward the elucidation of the CD44-ICD function by using a CD44-ICD-specific antibody, a modification of a ChIP assay to detect small molecules, and extensive computational analysis. We show that CD44-ICD translocates into the nucleus, where it then binds to a novel DNA consensus sequence in the promoter region of the MMP-9 gene to regulate its expression. We also show that the expression of many other genes that contain this novel response element in their promoters is up- or down-regulated by CD44-ICD. Furthermore, hypoxia-inducible factor-1α (Hif1α)-responsive genes also have the CD44-ICD consensus sequence and respond to CD44-ICD induction under normoxic conditions and therefore independent of Hif1α expression. Additionally, CD44-ICD early responsive genes encode for critical enzymes in the glycolytic pathway, revealing how CD44 could be a gatekeeper of the Warburg effect (aerobic glycolysis) in cancer cells and possibly cancer stem cells. The link of CD44 to metabolism is novel and opens a new area of research not previously considered, particularly in the study of obesity and cancer. In summary, our results finally give a function to the CD44-ICD and will accelerate the study of the regulation of many CD44-dependent genes.

Susceptibility to COVID-19 Nutrition Misinformation and Eating Behavior Change during Lockdowns: An International Web-Based Survey.

To understand the susceptibility to nutrition-health misinformation related to preventing, treating, or mitigating the risk of COVID-19 during the initial lockdowns around the world, the present international web-based survey study (15 April-15 May 2020) gauged participants' (n = 3707) level of nutrition-health misinformation discernment by presenting them with 25 statements (including unfounded or unproven claims circulated at the time), alongside the influence of information sources of varying quality on the frequency of changes in their eating behavior and the extent of misinformation held, depending on the source used for such changes. Results revealed widespread misinformation about food, eating, and health practices related to COVID-19, with the 25 statements put to participants receiving up to 43% misinformed answers (e.g., 'It is safe to eat fruits and vegetables that have been washed with soap or diluted bleach'). Whereas higher quality information sources (nutrition scientists, nutrition professionals) had the biggest influence on eating behavior change, we found greater misinformation susceptibility when relying on poor quality sources for changing diet. Appropriate discernment of misinformation was weakest amongst participants who more frequently changed their eating behavior because of information from poor quality sources, suggesting disparities in the health risks/safety of the changes performed.

The final frontier: what is distinctive about the bioethics of space missions? The cases of human enhancement and human reproduction.

We examine the bioethical issues that arise from long-duration space missions, asking what there is that is distinctive about such issues. We pay particular attention to the possibility that such space missions, certainly if they lead to self-sustaining space settlements, may require human enhancement, and examine the significance of reproduction in space for bioethics. We conclude that while space bioethics raises important issues to do with human survival and reproduction in very hazardous environments, it raises no issues that are distinct from those in terrestrial bioethics. Rather, space bioethics raises extreme versions of bioethical issues that are already found in the military, when working in extreme environments (such as Antarctica), or when living in circumstances (such as in prison) where one's autonomy is severely curtailed.

Evolutionary stasis: creationism, evolution and climate change in the Accelerated Christian Education curriculum.

There has been little consideration in the science education literature of schools or curricula that advocate creationism. Accelerated Christian Education (ACE) is among the world's largest providers of creationist science materials with a curriculum divided into a system of workbooks which students complete at their own speed. This article examines the ways in which ACE presents particular areas of science that it considers to be contentious, namely evolution and climate change. The ACE curriculum has recently been rewritten, and we show that, like previous editions, the current curriculum relies on rote memorisation to the exclusion of other styles of learning, and that information presented is often misleading or distorted. Religious explanations of natural phenomena are sometimes given in place of scientific ones, and creationist assumptions are inserted into lessons not directly related to evolution or the Big Bang. Those who reject creationism are depicted as making an immoral choice. ACE's recent curricula also add material denying the role of humans in climate change. It is argued that both the teaching methods and content of the ACE curriculum place students at an educational disadvantage.

Factors affecting physicians' attitudes towards patient-centred care: a cross-sectional survey in Beijing.

OBJECTIVES: Patient-centred care has been raised as an important component in providing high-quality healthcare services. This research aims to measure physicians' attitudes towards patient-centred care in Chinese healthcare settings and to identify the sociodemographic predictors of their attitudes using an exploratory research design. DESIGN: A cross-sectional survey. SETTING: Twelve hospitals in Beijing, China. PARTICIPANTS: 1290 physicians from 12 hospitals in Beijing were invited to take part in the survey using snowball sampling methods. There was a response rate of 84% (n=1084), of which 1053 responses (82%) were valid and included in this research. METHODS: This research used a survey containing a previously validated 6-point Likert scale called 'Chinese-revised Patient-Practitioner Orientation Scale' (CR-PPOS). Descriptive statistics and multivariable logistic regression analyses were performed to measure participants' attitudes and to identify the sociodemographic predictors of Chinese physicians' attitudes towards patient-centred care. RESULTS: Gender, professional title (ie, seniority) and hospital type influence Chinese physicians' attitudes towards patient-centred care. Female physicians, physicians with intermediate titles and those who work in tertiary (ie, top-level) hospitals tend to have higher patient-centred attitudes (OR=1.532, 95% CI 1.160 to 2.022; OR=2.089, 95% CI 1.206 to 3.618; OR=2.198, 95% CI 1.465 to 3.297) than male physicians with other titles, and than those who work in first, secondary or private hospitals. Physicians working in non-surgical departments, those who have received training in doctor-patient communication, and those who are satisfied with their income obtained high patient-centred scores, both on the overall CR-PPOS and its two subscales. CONCLUSIONS: This research identified sociodemographic predictors of Chinese physicians' attitudes towards patient-centred care. The findings contribute to knowledge of factors to be considered in reforming medical education and the Chinese healthcare system to improve physician-patient relationships and provide high-quality healthcare to patients. However, these findings are exploratory in nature and require further investigation to establish their validity and generalisability.

Diet-Nutrition Information Seeking, Source Trustworthiness, and Eating Behavior Changes: An International Web-Based Survey.

To understand the extent to which different sources of diet and nutrition information are sought, trusted, and relied upon for making dietary changes, the present international web-based survey study gauged participants' (n = 3419) diet-nutrition information-seeking behaviors from 22 interpersonal and general sources with varying quality, trust levels in these sources, and reliance on each source for making dietary changes. Qualitative insights were also captured regarding trustworthiness formation. The results revealed a disconnect between source popularity and perceived trustworthiness. While nutrition-health websites, Google-Internet searches, and diet-health books were most commonly consulted, participants placed the highest level of trust in nutrition scientists, nutrition professionals, and scientific journals, suggesting that frequent information seeking from a subpar source may not be a reliable predictor of the level of trust assigned to it. Although the frequency of source-seeking behaviors and source trustworthiness both contributed to dietary changes, the latter appeared to have a more pronounced influence. When a source was less trusted, there was a reduced likelihood of relying on it for changing diet. Additionally, source seeking may not always translate into effective dietary change, as shown by the less strong correlation between the two. These associations significantly differed depending on the source.

Reproductive health education in the schools of the four UK nations: is it falling through the gap?

Reproductive health education is crucial to ensure young people understand their reproductive system and can make informed decisions about their sexual lives and fertility, including whether they want to have children or not. This study involved an investigation of the intended UK school curricula for 14-18 year-olds as they relate to reproductive health. Analysis revealed substantial differences. Most, but not all, specifications include sexually transmitted infections, hormonal aspects of reproduction, contraception, the menstrual cycle and assisted reproductive technology (ART). Important topics, such as endometriosis, fertility, preconception health, pregnancy, miscarriage, menopause and infertility (except in the context of ART) are missing from examination specifications and/or the RSE/RSHP curricula. We conclude that many young people in the UK are at risk of leaving school with inadequate understanding of concepts that have important implications for their reproductive health. There are differences between nations, with Scotland having the most comprehensive coverage of topics in its curriculum. High-quality reproductive health education should be an entitlement for all young people. It should give young people accurate and up-to-date information and enable them to discuss issues and develop their own thinking. Ideally, sex and reproductive health education would be taught comprehensively across the RSE/RSHP and science curricula.