Two-dimensional correlated spectroscopy records reduced neurotransmission in blast-exposed artillery soldiers after live fire training.

There is a requirement for an objective method to determine a safe level of low-level military occupational blast, having recognised it can lead to neurological damage. The purpose of the current study was to evaluate the effect of artillery firing training on the neurochemistry of frontline soldiers using two-dimensional (2D) COrrelated SpectroscopY (2D COSY) in a 3-T clinical MR scanner. Ten men considered to be of sound health were evaluated before and after a week-long live firing exercise in two ways. Prior to the live fire exercise, all participants were screened by a clinical psychologist using a combination of clinical interviews and psychometric tests, and were then scanned with 3-T MRI. The protocols included T1- and T2-weighted images for diagnostic reporting and anatomical localisation and 2D COSY to record any neurochemical effects from the firing. No changes to the structural MRI were recorded. Nine substantive and statistically significant changes in the neurochemistry were recorded as a consequence of firing training. Glutamine and glutamate, glutathione, and two of the seven fucose-α (1-2)-glycans were significantly increased. N-acetyl aspartate, myo-inositol + creatine, and glycerol were also increased. Significant decreases were recorded for the glutathione cysteine moiety and tentatively assigned glycan with a 1-6 linkage (F2: 4.00, F1: 1.31 ppm). These molecules are part of three neurochemical pathways at the terminus of the neurons providing evidence of early markers of disruption to neurotransmission. Using this technology, the extent of deregulation can now be monitored for each frontline defender on a personalised basis. The capacity to monitor early a disruption in neurotransmitters, using the 2D COSY protocol, can observe the effect of firing and may be used to prevent or limit these events.

The allometry of mitochondrial efficiency is tissue dependent: a comparison between skeletal and cardiac muscles of birds.

Body mass is known to be a fundamental driver of many biological traits, including metabolism. However, the effect of body mass on mitochondrial energy transduction is still poorly understood and has mainly been described in mammals. Using 13 species of birds ranging from 15 g (finches) to 160 kg (ostrich), we report here that the mitochondrial production of ATP, and the corresponding oxygen consumption, are negatively dependent on body mass in skeletal muscles but not in the heart. Results also showed that mitochondrial efficiency was positively correlated with body mass at sub-maximal phosphorylating states in the skeletal muscle, but not in the heart. This difference between muscle tissues is potentially linked to the difference in energetic demand expandability and the heavy involvement of skeletal muscle in thermoregulation.

Meta-analysis of primary care delivered buprenorphine treatment retention outcomes.

Background: Currently, the capacity to provide buprenorphine treatment (BT) is not sufficient to treat the growing number of people in the United States with opioid use disorder (OUD). We sought to examine participant retention in care rates of primary care delivered BT programs and to describe factors associated with retention/attrition for participants receiving BT in this setting.Objectives: A PRISMA-guided search of various databases was performed to identify the articles focusing on efficacy of BT treatment and OUD.Method: A systematic literature search identified 15 studies examining retention in care in the primary care setting between 2002 and 2020. Random effects meta-regression were used to identify retention rates across studies.Results: Retention rates decreased across time with a mean 0.52 rate at one year. Several factors were found to be related to retention, including: race, use of other drugs, receipt of counseling, and previous treatment with buprenorphine.Conclusions: While we only investigate BT through primary care, our findings indicate retention rates are equivalent to the rates reported in the specialty care literature. More work is needed to examine factors that may impact primary care delivered BT specifically and differentiate participants that may benefit from care delivered in specialty over primary care as well as the converse.

Transcriptionally dynamic progenitor populations organised around a stable niche drive axial patterning.

The elongating mouse anteroposterior axis is supplied by progenitors with distinct tissue fates. It is not known whether these progenitors confer anteroposterior pattern to the embryo. We have analysed the progenitor population transcriptomes in the mouse primitive streak and tail bud throughout axial elongation. Transcriptomic signatures distinguish three known progenitor types (neuromesodermal, lateral/paraxial mesoderm and notochord progenitors; NMPs, LPMPs and NotoPs). Both NMP and LPMP transcriptomes change extensively over time. In particular, NMPs upregulate Wnt, Fgf and Notch signalling components, and many Hox genes as progenitors transit from production of the trunk to the tail and expand in number. In contrast, the transcriptome of NotoPs is stable throughout axial elongation and they are required for normal axis elongation. These results suggest that NotoPs act as a progenitor niche whereas anteroposterior patterning originates within NMPs and LPMPs.

Breast Tissue Chemistry Measured In Vivo In Healthy Women Correlate with Breast Density and Breast Cancer Risk.

BACKGROUND: The relationship of tissue chemistry to breast density and cancer risk has not been documented despite breast density being a known risk factor. PURPOSE: To investigate whether distinct chemical profiles associated with breast density and cancer risk are identified in healthy breast tissue using in vivo two-dimensional correlated spectroscopy (2D COSY). STUDY TYPE: Prospective. POPULATION: One-hundred-seven participants including 55 at low risk and 52 at high risk of developing breast cancer. FIELD STRENGTH/SEQUENCE: 3 T/ axial/ T1, T2, 2D COSY. ASSESSMENT: Two radiologists defined breast density on T2. Interobserver variability assessed. Peak volumes normalized to methylene at (1.30, 1.30) ppm as internal shift reference. STATISTICAL TESTS: Chi-squared/Mann-Whitney/Kappa statistics/Kruskal Wallis/pairwise analyses. Significance level 0.05. RESULTS: Ten percentage were fatty breasts, 39% scattered fibroglandular, 35% heterogeneously dense, and 16% extremely dense. Interobserver variability was excellent (kappa = 0.817). Sixty percentage (64/107) were premenopausal. Four distinct tissue chemistry categories were identified: low-density (LD)/premenopausal, high-density (HD)/premenopausal, LD/postmenopausal, and HD/postmenopausal. Compared to LD, HD breast chemistry showed significant increases of cholesterol (235%) and lipid unsaturation (33%). In the low-risk category, postmenopausal women with dense breasts recorded the largest significant changes including cholesterol methyl 540%, lipid unsaturation 207%, glutamine/glutamate 900%, and choline/phosphocholine 800%. In the high-risk cohort, premenopausal women with HD recorded a more active chemical profile with significant increases in choline/phosphocholine 1100%, taurine/glucose 550% and cholesterol sterol 250%. DATA CONCLUSION: Four distinct chemical profiles were identified in healthy breast tissue based on breast density and menopausal status in participants at low and high risk. Gradual increase in neutral lipid content and metabolites was noted in both risk groups across categories in different order. In low risk, the HD postmenopausal category exhibited the highest metabolic activity, while women at high risk exhibited the highest lipid content and metabolic activity in the HD premenopausal category. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

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.

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.

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.

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.

BACKGROUND: 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. AIMS: To establish whether GABA, glutamate, glutamine and Glx levels differ across pain conditions when compared to pain-free controls. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Out of the Closet, Into the Clinic: Opportunities for Expanding Men Who Have Sex With Men-Competent Services in China.

BACKGROUND: Despite the high human immunodeficiency virus (HIV) burden among men who have sex with men (MSM), there is little research on health services provided to MSM in China and other low- and middle-income countries. Discrimination and inadequate services may discourage MSM from seeking health care services. This study examined essential services provided to MSM and health care discrimination among MSM in China. METHODS: A nationwide cross-sectional online survey was conducted among MSM who saw a physician in the last 24 months in China. The survey included items on sociodemographic information, HIV testing, experiences from the last physician encounter, and history of perceived health care discrimination. We defined MSM-competent physicians as physicians who asked their patient about having sex with other men, asked about anal sex, and either asked about or recommended HIV testing at the most recent visit. RESULTS: Among the 503 participants, 35.0% (176/503) saw an MSM-competent physician. In multivariate analyses, respondents who saw an MSM-competent physician were more likely to be younger (adjusted odds ratio [AOR], 0.87; 95% confidence interval [CI], 0.81-0.94), have a primary care physician (AOR, 3.24; 95% CI, 1.85-5.67), and be living with HIV (AOR, 2.01; 95% CI, 1.13-3.56). 61.2% (308/503) of MSM had ever experienced health care discrimination. CONCLUSIONS: Our data suggest that there is variability in the extent to which physicians are meeting the needs of MSM in China. There is an urgent need to evaluate and expand MSM-competent services in China.

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.

Direct Interactions Between Gli3, Wnt8b, and Fgfs Underlie Patterning of the Dorsal Telencephalon.

A key step in the development of the cerebral cortex is a patterning process, which subdivides the telencephalon into several molecularly distinct domains and is critical for cortical arealization. This process is dependent on a complex network of interactions between signaling molecules of the Fgf and Wnt gene families and the Gli3 transcription factor gene, but a better knowledge of the molecular basis of the interplay between these factors is required to gain a deeper understanding of the genetic circuitry underlying telencephalic patterning. Using DNA-binding and reporter gene assays, we here investigate the possibility that Gli3 and these signaling molecules interact by directly regulating each other's expression. We show that Fgf signaling is required for Wnt8b enhancer activity in the cortical hem, whereas Wnt/ß-catenin signaling represses Fgf17 forebrain enhancer activity. In contrast, Fgf and Wnt/ß-catenin signaling cooperate to regulate Gli3 expression. Taken together, these findings indicate that mutual interactions between Gli3, Wnt8b, and Fgf17 are crucial elements of the balance between these factors thereby conferring robustness to the patterning process. Hence, our study provides a framework for understanding the genetic circuitry underlying telencephalic patterning and how defects in this process can affect the formation of cortical areas.

Performance-based incentives to improve health status of mothers and newborns: what does the evidence show?

Performance-based incentives (PBIs) aim to counteract weak providers' performance in health systems of many developing countries by providing rewards that are directly linked to better health outcomes for mothers and their newborns. Translating funding into better health requires many actions by a large number of people. The actions span from community to the national level. While different forms of PBIs are being implemented in a number of countries to improve health outcomes, there has not been a systematic review of the evidence of their impact on the health of mothers and newborns. This paper analyzes and synthesizes the available evidence from published studies on the impact of supply-side PBIs on the quantity and quality of health services for mothers and newborns. This paper reviews evidence from published and grey literature that spans PBI for public-sector facilities, PBI in social insurance reforms, and PBI in NGO contracting. Some initiatives focus on safe deliveries, and others reward a broader package of results that include deliveries. The Evidence Review Team that focused on supply-side incentives for the US Government Evidence Summit on Enhancing Provision and Use of Maternal Health Services through Financial Incentives, reviewed published research reports and papers and added studies from additional grey literature that were deemed relevant. After collecting and reviewing 17 documents, nine studies were included in this review, three of which used before-after designs; four included comparison or control groups; one applied econometric methods to a five-year time series; and one reported results from a large-scale impact evaluation with randomly-assigned intervention and control facilities. The available evidence suggests that incentives that reward providers for institutional deliveries result in an increase in the number of institutional deliveries. There is some evidence that the content of antenatal care can improve with PBI. We found no direct evidence on the impact of PBI on neonatal health services or on mortality of mothers and newborns, although intention of the study was not to document impact on mortality. A number of studies describe approaches to rewarding quality as well as increases in the quantities of services provided, although how quality is defined and monitored is not always clear. Because incentives exist in all health systems, considering how to align the incentives of the many health workers and their supervisors so that they focus efforts on achieving health goals for mothers and newborns is critical if the health system is to perform more effectively and efficiently. A wide range of PBI models is being developed and tested, and there is still much to learn about what works best. Future studies should include a larger focus on rewarding quality and measuring its impact. Finally, more qualitative research to better understand PBI implementation and how various incentive models function in different settings is needed to help practitioners refine and improve their programmes.

Adipokines in obesity and metabolic-related-diseases.

The discovery of leptin in the 1990s led to a reconsideration of adipose tissue (AT) as not only a fatty acid storage organ, but also a proper endocrine tissue. AT is indeed capable of secreting bioactive molecules called adipokines for white AT or batokines for brown/beige AT, which allow communication with numerous organs, especially brain, heart, liver, pancreas, and/or the vascular system. Adipokines exert pro or anti-inflammatory activities. An equilibrated balance between these two sets ensures homeostasis of numerous tissues and organs. During the development of obesity, AT remodelling leads to an alteration of its endocrine activity, with increased secretion of pro-inflammatory adipokines relative to the anti-inflammatory ones, as shown in the graphical abstract. Pro-inflammatory adipokines take part in the initiation of local and systemic inflammation during obesity and contribute to comorbidities associated to obesity, as detailed in the present review.

Addiction to a bad idea, especially in low- and middle-income countries: Contributory health insurance.

Despite limited evidence of successful development and implementation of contributory health insurance and low and middle income countries, many countries are in the process implementing such schemes. This commentary summarizes all available evidence on the limitations of contributory health insurance including the lack of good theoretical underpinning and the considerable evidence of inequity and fragmentation created by such schemes. Moreover, the initiation of a contributory health insurance scheme has not been found to increase revenues to the health sector or help health countries achieve universal health coverage. Low and middle income countries can improve equity and efficiency of the health sector by replacing out-of-pocket spending with pre-paid pooling mechanisms, but that is best done through budget transfers and not by contributory insurance that links payment to sub-population entitlements.

Case Report: Capacity to Objectively Monitor the Response of a Chronic Pain Patient to Treatment.

Response to pain therapy is currently by patient self-report. We demonstrate that by evaluating the neurochemistry of a patient, using two-dimensional Correlated SpectroscopY (2D COSY) in a 3T MRI scanner, response to therapy can be recorded. A chronic temporomandibular joint (TMJ) pain patient was evaluated by a pain physician specializing in temporomandibular disorders (TMD), and by 2D COSY, before, and 6 days after treatment with Botulinum Toxin A. Prior to treatment the self-reported pain score was 8/10 and reduced to 0/10 within 24 h of treatment. The neurochemistry of the patient prior to treatment was typical of chronic pain. In particular, the Fuc-α(1-2) glycans were affected. Following treatment, the substrates, α-L Fucose, were elevated and the Fuc-α(1-2) glycans repopulated. The depletion of the molecule assigned the glutathione cysteine moiety, with chronic pain, is indicative of a Glutathione redox imbalance linked to neurodegeneration. This new approach to monitor pain could help discriminate the relative contributions in the complex interplay of the sensory and affective (emotional suffering) components of pain leading to appropriate individualized pharmaceutical drug regimens.

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.

SAR studies on dihydropyrimidinone antibiotics.

There is an urgent need for the development of novel antimicrobial agents that offer effective treatment against MRSA. Using a new class of dipeptide antibiotic TAN-1057A/B as lead, we designed, synthesized and evaluated analogs of TAN-1057A/B. Several novel dihydropyrimidinone antibiotics demonstrating comparable antibiotic efficacy while possessing favorable selectivity were identified.

Making Health Insurance Pro-poor: Lessons from 20 Developing Countries.

The last 20 years have seen a substantial growth in research on the extent to which health sector reforms are pro-poor or pro-rich. What has been missing is knowledge synthesis work to derive operational lessons from the empirical research. This article fills the gap for the most popular form of health financing reform, health insurance. Based on publications covering 20 developing countries, we find that health insurance is no panacea for improving equity in the health sector. More importantly, we find certain design elements of health insurance can increase the likelihood of tackling inequality in the health sector in developing countries.