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My week with Marilyn
In the summer of 1956, 23-year-old Colin Clark, determined to make his way in the film business, worked as a lowly assistant on the set of The Prince and the Showgirl, the film that famously united Sir Laurence Olivier and Marilyn Monroe. When his diary account was published, one week was missing. This is the story of that week: an idyll in which he escorted a Monroe desperate to get away from Hollywood hangers-on and the pressures of work.
DVD
Brain GABA and glutamate levels across pain conditions: A systematic literature review and meta-analysis of 1H-MRS studies using the MRS-Q quality assessment tool
A proposed mechanism of chronic pain is dysregulation between the main inhibitory (GABA) and excitatory (glutamate) neurometabolites of the central nervous system. The level of these neurometabolites appears to differ in individual studies of people with pain compared to pain-free controls across different pain conditions. However, this has yet to be systematically investigated.
To establish whether GABA, glutamate, glutamine and Glx levels differ across pain conditions when compared to pain-free controls.
Five databases were searched. Studies were included if they investigated: 1) A pain condition compared to control. 2) Reported GABA, glutamate, glutamine or glutamate/glutamine level. 3) Used 1H-Magnetic Resonance Spectroscopy (Prospero Project ID CRD42018092170). Data extracted included neurometabolite level, pain diagnosis, and spectroscopy parameters. Meta-analyses were conducted to establish the difference in neurometabolite level between participants with pain and pain-free controls for different pain conditions. The MRS-Q was developed from existing clinical consensus to allow for the assessment of quality in the included studies.
Thirty-five studies were included investigating combinations of migraine (n = 11), musculoskeletal pain (n = 8), chronic pain syndromes (n = 9) and miscellaneous pain (n = 10). Higher GABA levels were found in participants with migraine compared to controls (Hedge's G 0.499, 95%CI: 0.2 to 0.798). In contrast, GABA levels in musculoskeletal pain conditions (Hedge's G −0.189, 95%CI: 0.530 to 0.153) and chronic pain syndromes (Hedge's G 0.077, 95%CI: 1.612 to 1.459) did not differ from controls. Results for other brain neurometabolites revealed significantly higher levels for glutamate in participants with migraine and Glx in chronic pain syndromes compared to controls.
These results support the theory that underlying neurometabolite levels may be unique in different pain conditions and therefore representative of biomarkers for specific pain conditions.
•Meta-analysis of excitatory and inhibitory neurometabolites across pain conditions.•Introduces the new Magnetic Resonance Spectroscopy quality assessment tool (MRS-Q).•GABA, Glutamate, Glutamine and Glx concentrations appear unique to pain conditions.•Provides key knowledge to inform biomarker research in headaches and pain.•Findings highlight need to improve reporting in spectroscopy literature.
Journal Article
Nessys: A new set of tools for the automated detection of nuclei within intact tissues and dense 3D cultures
Methods for measuring the properties of individual cells within their native 3D environment will enable a deeper understanding of embryonic development, tissue regeneration, and tumorigenesis. However, current methods for segmenting nuclei in 3D tissues are not designed for situations in which nuclei are densely packed, nonspherical, or heterogeneous in shape, size, or texture, all of which are true of many embryonic and adult tissue types as well as in many cases for cells differentiating in culture. Here, we overcome this bottleneck by devising a novel method based on labelling the nuclear envelope (NE) and automatically distinguishing individual nuclei using a tree-structured ridge-tracing method followed by shape ranking according to a trained classifier. The method is fast and makes it possible to process images that are larger than the computer's memory. We consistently obtain accurate segmentation rates of >90%, even for challenging images such as mid-gestation embryos or 3D cultures. We provide a 3D editor and inspector for the manual curation of the segmentation results as well as a program to assess the accuracy of the segmentation. We have also generated a live reporter of the NE that can be used to track live cells in 3 dimensions over time. We use this to monitor the history of cell interactions and occurrences of neighbour exchange within cultures of pluripotent cells during differentiation. We provide these tools in an open-access user-friendly format.
Journal Article
Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction
The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals.
Journal Article
Five years of #MedRadJClub: An impact evaluation of an established twitter journal club
Introduction
Twitter journal clubs are a relatively new adaptation of an established continuing professional development (CPD) activity within healthcare. The medical radiation science (MRS) journal club ‘MedRadJClub’ (MRJC) was founded in March 2015 by a group of academics, researchers and clinicians as an international forum for the discussion of peer‐reviewed papers. To investigate the reach and impact of MRJC, a five‐year analysis was conducted.
Methods
Tweetchat data (number of participants, tweets and impressions) for the first five years of MRJC were extracted and chat topics organised into themes. Fifth anniversary MRJC chat tweets were analysed and examples of academic and professional outputs were collated.
Results
A total of 59 chats have been held over five years with a mean of 41 participants and 483,000 impressions per hour‐long synchronous chat. Ten different tweetchat themes were identified, with student engagement/preceptorship the most popular. Eight posters or oral presentations at conferences, one social media workshop and four papers have been produced. Qualitative analysis revealed five core themes relating to the perceived benefits of participation in MRJC: (1) CPD and research impact, (2) professional growth and influencing practice, (3) interdisciplinary learning and inclusion, (4) networking and social support and (5) globalisation.
Conclusion
MRJC is a unique, multi‐professional, global community with consistent engagement. It is beneficial for both CPD, research engagement, dissemination and socialisation within the MRS community.
The medical radiation science (MRS) journal club (MRJC) was founded in March 2015 as an international forum for the discussion of peer‐reviewed papers. To investigate the reach and impact of MRJC, a five‐year analysis was conducted. Results demonstrate that MRJC is a unique, multi‐professional, global community with consistent engagement and is beneficial for both CPD, research engagement, dissemination and socialisation within the MRS community.
Journal Article
Synthetic Biology: State Regulation in the Biomedical Context
Synthetic biology is an emerging, interdisciplinary research field with much promise for biomedicine. Broadly defined as “the design and construction of new biological systems to perform specific tasks,” researchers and clinicians are using synthetic biology to develop targeted treatments for cancer, coronaviruses, and so forth. Because of the experimental nature of synthetic biology, regulation is necessary. Current federal frameworks, such as the Food, Drug, and Cosmetics Act, The Toxic Substances Act of 1976, Institutional Review Boards, and self-regulation are not enough. As a result, states have a unique opportunity to develop statutory and regulatory frameworks to develop a pathway for regulating synthetic biology. In developing legislation, state lawmakers should look to build a comprehensive framework that addresses businesses selling technology for synthesizing DNA codes, monitors orders for synthetic DNA, and develops statewide documentation systems. Additionally, public health information on treatments using synthetic biology can help to educate the public and reduce the prevalence of misconceptions about the technology. In the absence of federal regulation, states should step into the synthetic biology regulatory space to ensure that their citizens are not harmed by therapies developed using synthetic biology.
Journal Article
The Effects of Perceived Stress and Cortisol Concentration on Antiretroviral Adherence When Mediated by Psychological Flexibility Among Southern Black Men Living with HIV
This pilot study investigates the correlation between psychological stress and antiretroviral therapy (ART) adherence and plasma HIV RNA (viral load) as mediated by psychological flexibility among Black men in the south. Data were collected from 48 HIV-positive, low income Black men. Results indicate a strong positive correlation between perceived stress and psychological inflexibility (adjusted for age and income rs = 0.67; p < 0.001), a negative correlation between psychological inflexibility and ART adherence (adjusted rs = − 0.32; p = 0.03), a negative correlation between perceived stress and ART adherence (adjusted rs = − 0.45; p = 0.006), and a negative correlation between ART adherence and viral load (adjusted rs = − 0.37; p = 0.04). Our findings suggest stress decreases adherence to ART and viral suppression among Black men living with HIV. However, psychological flexibility did not mediate the relationship between stress and treatment adherence. Hair cortisol concentrations were high (mean of 34.2 pg/mg), but uncorrelated with adherence.
Journal Article
Linking young men who have sex with men (YMSM) to STI physicians: a nationwide cross-sectional survey in China
Background
Many young men who have sex with men (YMSM) are reluctant to seek health services and trust local physicians. Online information seeking may encourage YMSM to identify and see trustworthy physicians, obtain sexual health services, and obtain testing for sexually transmitted infections (STIs). This study examined online STI information seeking behaviors among Chinese YMSM and its association with offline physician visits.
Methods
We conducted a nationwide online survey among YMSM through WeChat, the largest social media platform in China. We collected information on individual demographics, sexual behaviors, online STI information seeking, offline STI testing, and STI physician visits. We examined the most commonly used platforms (search engines, governmental websites, counseling websites, generic social media, gay mobile apps, and mobile medical apps) and their trustworthiness. We assessed interest and willingness to use an MSM-friendly physician finder function embedded within a gay mobile app. Logistic regression models were used to examine the correlation between online STI information searching and offline physician visits.
Results
A total of 503 men completed the survey. Most men (425/503, 84.5%) searched for STI information online. The most commonly used platform to obtain STI information were search engines (402/425, 94.5%), followed by gay mobile apps (201/425, 47.3%). Men reported high trustworthiness of information received from gay mobile apps. Men also reported high interest (465/503, 92.4%) and willingness (463/503, 92.0%) to use a MSM-friendly physician finder function within such apps. Both using general social media (aOR =1.14, 95%CI: 1.04–1.26) and mobile medical apps (aOR =1.16, 95%CI: 1.01–1.34) for online information seeking were associated with visiting a physician.
Conclusion
Online STI information seeking is common and correlated with visiting a physician among YMSM. Cultivating partnerships with the emerging mobile medical apps may be useful for disseminating STI information and providing better physician services to YMSM.
Journal Article