Health by design; optimising our urban environmental microbiomes for human health.

Humans have evolved in direct and intimate contact with their environment and the microbes that it contains, over a period of 2 million years. As a result, human physiology has become intrinsically linked to environmental microbiota. Urbanisation has reduced our exposure to harmful pathogens, however there is now increasing evidence that these same health-protective improvements in our environment may also be contributing to a hidden disease burden: immune dysregulation. Thoughtful and purposeful design has the potential to ameliorate these health concerns by providing sources of microbial diversity for human exposure. In this narrative review, we highlight the role of environmental microbiota in human health and provide insights into how we can optimise human health through well-designed cities, urban landscapes and buildings. The World Health Organization recommends there should be at least one public green space of least 0.5 ha in size within 300m of a place of residence. We argue that these larger green spaces are more likely to permit functioning ecosystems that deliver ecosystem services, including the provision of diverse aerobiomes. Urban planning must consider the conservation and addition of large public green spaces, while landscape design needs to consider how to maximise environmental, social and public health outcomes, which may include rewilding. Landscape designers need to consider how people use these spaces, and how to optimise utilisation, including for those who may experience challenges in access (e.g. those living with disabilities, people in residential care). There are also opportunities to improve health via building design that improves access to diverse environmental microbiota. Considerations include having windows that open, indoor plants, and the relationship between function, form and organization. We emphasise possibilities for re-introducing potentially health-giving microbial exposures into urban environments, particularly where the benefits of exposure to biodiverse environments may have been lost.

ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Forest Restoration and the Zoonotic Vector Anopheles balabacensis in Sabah, Malaysia.

Anthropogenic changes to forest cover have been linked to an increase in zoonotic diseases. In many areas, natural forests are being replaced with monoculture plantations, such as oil palm, which reduce biodiversity and create a mosaic of landscapes with increased forest edge habitat and an altered micro-climate. These altered conditions may be facilitating the spread of the zoonotic malaria parasite Plasmodium knowlesi in Sabah, on the island of Borneo, through changes to mosquito vector habitat. We conducted a study on mosquito abundance and diversity in four different land uses comprising restored native forest, degraded native forest, an oil palm estate and a eucalyptus plantation, these land uses varying in their vegetation types and structure. The main mosquito vector, Anopheles balabacensis, has adapted its habitat preference from closed canopy rainforest to more open logged forest and plantations. The eucalyptus plantations (Eucalyptus pellita) assessed in this study contained significantly higher abundance of many mosquito species compared with the other land uses, whereas the restored dipterocarp forest had a low abundance of all mosquitos, in particular, An. balabacensis. No P. knowlesi was detected by PCR assay in any of the vectors collected during the study; however, P. inui, P. fieldi and P. vivax were detected in An. balabacensis. These findings indicate that restoring degraded natural forests with native species to closed canopy conditions reduces abundance of this zoonotic malarial mosquito vector and therefore should be incorporated into future restoration research and potentially contribute to the control strategies against simian malaria.

Patient-related barriers and enablers to the implementation of high-value physiotherapy for chronic pain: a systematic review.

OBJECTIVE: To identify and synthesize patient-related barriers to and enablers of the implementation of high-value physiotherapy (HVP) for chronic pain. Furthermore, to review what patient-related interventions have been used to facilitate the implementation of HVP for chronic pain, as well as their efficacy. METHODS: We systematically searched the APA PsycInfo, Embase, CINAHL, Medline, Scopus, and PEDro databases for peer-reviewed studies (published in English) of adults with chronic pain. We used the Theoretical Domains Framework of behavior change to synthesize identified themes relating to barriers and enablers. Outcomes from studies reporting on interventions were also qualitatively synthesized. RESULTS: Fourteen studies reported on barriers and enablers, 8 of which related to exercise adherence. Themes common to barriers and enablers included perceived efficacy of treatment, interrelationship with the physiotherapist, exercise burden, and the patient's understanding of exercise benefits. Other barriers included fear of movement, fragmented care, and cost. Ten studies explored interventions, 9 of which aimed to improve exercise adherence. Of these, evidence from 4 randomized controlled trials of technology-based interventions demonstrated improved exercise adherence among intervention groups compared with controls. CONCLUSION: Patients with chronic pain experience barriers to HVP, including their beliefs, the nature of their interaction with their physiotherapist, perceived treatment efficacy, and cost. Enablers include rapport with their physiotherapist, achievable exercises, and seamless cost-effective care. Technology-based interventions have demonstrated effectiveness at increasing exercise adherence. Our findings suggest that interventions seeking to enhance implementation of HVP need to consider the multifactorial barriers experienced by patients with chronic pain. STUDY REGISTRATION: Open Science Framework (https://doi.org/10.17605/OSF.IO/AYGZV).

Correction: Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

[This corrects the article DOI: 10.1371/journal.pone.0265254.].

Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study.

OBJECTIVE: Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database. METHODS: The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality. RESULTS: The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery-related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non-spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery. CONCLUSIONS: Initiation of LMWH within 24 hours was associated with a low rate of spine surgery-related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.

What are green prescriptions? A scoping review.

Introduction Clear terminology is critical to allow accurate communication between practitioners, policy makers and the public. Aim We investigated how the term 'green prescription' has been used in the peer-reviewed literature. Methods We conducted a scoping review of the peer-reviewed literature that used the term 'green prescription(s)' and determined how this term was used. We then investigated how the term has been used over time, in different geographic locations and in different academic disciplines. Results We included 268 articles that used the term 'green prescription(s)'. We found that the phrase 'green prescription(s)' has been used since 1997 to mean a written prescription for a lifestyle change, most commonly physical activity, provided by a health practitioner. However, more recently (since 2014) the term has also been used to mean exposure to nature. Despite the emergence of this new meaning, 'green prescription' remains, in the health and medical science literature across all continents, most commonly used to describe a prescription for physical activity. Conclusion The use of the term 'green prescriptions' is inconsistent and has led to misuse of the research evidence regarding written prescriptions for exercise/diet being used to justify nature exposure to improve human health. We recommend that the term 'green prescriptions' continues to be used only as per its original definition, to refer to written prescriptions for physical activity and/or diet. For prescriptions to spend time in nature, we suggest use of the more appropriate term 'nature prescriptions'.

Will the increased use of ring lights during the coronavirus pandemic lead to a growing burden of macular degeneration?

The pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has brought with it many changes in the way with live, work, and socialise. One such change is an increase in the use of videoconferencing for communication with friends, family and work colleagues, and doing presentations, while physically distancing. We demonstrate an increase in the use of ring lights during the pandemic, and argue that this increased exposure to blue light may lead to a growing burden of macular degeneration in coming years.

Hypotension requiring vasopressor treatment and increased cardiac complications in elderly spinal cord injury patients: a prospective TRACK-SCI registry study.

OBJECTIVE: Increasing life expectancy has led to an older population. In this study, the authors analyzed complications and outcomes in elderly patients following spinal cord injury (SCI) using the established multi-institutional prospective study Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database collected in the Department of Neurosurgical Surgery at the University of California, San Francisco. METHODS: TRACK-SCI was queried for elderly individuals (≥ 65 years of age) with traumatic SCI from 2015 to 2019. Primary outcomes of interest included total hospital length of stay, perioperative complications, postoperative complications, and in-hospital mortality. Secondary outcomes included disposition location, and neurological improvement based on the American Spinal Injury Association Impairment Scale (AIS) grade at discharge. Descriptive analysis, Fisher's exact test, univariate analysis, and multivariable regression analysis were performed. RESULTS: The study cohort consisted of 40 elderly patients. The in-hospital mortality rate was 10%. Every patient in this cohort experienced at least 1 complication, with a mean of 6.6 separate complications (median 6, mode 4). The most common complication categories were cardiovascular, with a mean of 1.6 complications (median 1, mode 1), and pulmonary, with a mean of 1.3 (median 1, mode 0) complications, with 35 patients (87.5%) having at least 1 cardiovascular complication and 25 (62.5%) having at least 1 pulmonary complication. Overall, 32 patients (80%) required vasopressor treatment for mean arterial pressure (MAP) maintenance goals. The use of norepinephrine correlated with increased cardiovascular complications. Only 3 patients (7.5%) of the total cohort had an improved AIS grade compared with their acute level at admission. CONCLUSIONS: Given the increased frequency of cardiovascular complications associated with vasopressor use in elderly SCI patients, caution is warranted when targeting MAP goals in these patients. A downward adjustment of blood pressure maintenance goals and prophylactic cardiology consultation to select the most appropriate vasopressor agent may be advisable for SCI patients ≥ 65 years of age.

Critical appraisal in ecology: What tools are available, and what is being used in systematic reviews?

Many reviews referred to as 'systematic reviews' in ecology are not consistent with best practice in that they generally lack appropriate critical appraisal of included studies. This limitation is particularly important in applied ecology, where there have been increasing calls for more systematic reviews to guide decision making. To identify the available critical appraisal tools (CATs) and hierarchies of evidence available for ecology studies, we systematically searched for: studies that described the development and/or examination of tools to assess the potential methodological bias in studies of ecology; and the tools used to assess potential methodological bias of included studies in ecological systematic reviews. We identified 680 reviews labelled as 'systematic reviews' in ecology, however only 4.0% performed critical appraisal of the included studies. Three hierarchies of evidence and 23 CATs were identified, and assessed as lacking independent development, validity and reliability testing, and/or completeness. The authors of the reviews that included critical appraisal have appropriately identified the need to move reviews in ecology in the direction of this higher level of evidence, and have taken applied ecology further in the direction of evidence-based practice. However, we identified shortcomings in these approaches when compared with best practice, and conclude that new tools are needed that reflect a range of questions posed in ecology. Through increasing the availability of such tools, the strength of evidence provided by systematic reviews in ecology would improve.

Physiotherapy and ecosystem services: improving the health of our patients, the population, and the environment.

INTRODUCTION: The relevance of ecosystems to physiotherapy has traditionally been overlooked, despite its potential for health impacts relevant to conditions often managed by physiotherapists. PURPOSE: The purpose of this article is to introduce the concept of ecosystem services to physiotherapists, and to discuss how understanding ecosystem services may improve patient care, and population and planetary health. DISCUSSION AND CONCLUSION: Physiotherapists with an understanding of ecosystem services may improve patient care by value-adding to management through patient education, empathy, advocacy, and broader population health approaches. Physiotherapists are also well placed to promote the conservation and restoration of ecosystem through participation, advocacy, and the development of public health measures, to the benefit of global sustainability and population health. Further research is required into how physiotherapists currently use nature-based interventions, and the barriers and enablers to their use. To be adequately prepared to meet the challenges that climate change and environmental degradation pose to patient care, population health and health systems, both current and future physiotherapists need to take a broader view of their practice. By including consideration of the potential role of the environment and green space exposure in particular on their patient's health, physiotherapists can ultimately contribute more to population and planetary health.

Are music students at 'high-risk' of experiencing musculoskeletal symptom outcomes compared with other students?

Musicians have been described as a 'high-risk' group for experiencing musculoskeletal symptoms (MSSs), yet few studies have tested this assumption. We aimed to determine whether the prevalence and profile of MSS outcomes differed between university music students and a reference group (science students). A survey was conducted of university music and science students. Reported MSS outcomes among the two groups were compared using regression analyses. The majority of participants in both groups reported experiencing MSSs in the last 12 months and 7 days. Music students reported a higher prevalence of wrist/hand MSSs compared with science students. Compared with symptomatic science students, music students reported a higher emotional impact of MSSs. We recommend prioritizing research into interventions for music students that address MSSs in the wrist/hand region, and the emotional impact of MSSs. Addressing these MSS outcomes could reduce the MSS burden for musicians during and beyond their studies.

Ecosystem restoration is integral to humanity's recovery from COVID-19.

COVID-19 has devastated global communities and economies. The pandemic has exposed socioeconomic disparities and weaknesses in health systems worldwide. Long-term health effects and economic recovery are major concerns. Ecosystem restoration-ie, the repair of ecosystems that have been degraded-relates directly to tackling the health and socioeconomic burdens of COVID-19, because stable and resilient ecosystems are fundamental determinants of health and socioeconomic stability. Here, we use COVID-19 as a case study, showing how ecosystem restoration can reduce the risk of infection and adverse sequelae and have an integral role in humanity's recovery from COVID-19. The next decade will be crucial for humanity's recovery from COVID-19 and for ecosystem repair. Indeed, in the absence of effective, large-scale restoration, 95% of the Earth's land could be degraded by 2050. The UN Decade on Ecosystem Restoration (2021-30) declaration reflects the growing urgency and scale at which we should repair ecosystems. Importantly, ecosystem restoration could also help to combat the health and socioeconomic issues that are associated with COVID-19, yet it is poorly integrated into current responses to the disease. Ecosystem restoration can be a core public health intervention and assist in COVID-19 recovery if it is closely integrated with socioeconomic, health, and environmental policies.

Musculoskeletal Symptoms in Professional Musicians: Do Self-employed and Employer-employed Musicians Differ?

Concerns have been raised for the health and wellbeing of self-employed workers. Musicians are the 'original' gig workers, and musicians have a high prevalence of musculoskeletal symptoms (MSSs). Studies of musicians' MSSs have typically focused on classical, employer-employed musicians; leaving self-employed musicians under-investigated. We investigated the prevalence of MSS outcomes in all types of professional musicians, and compared the MSS outcomes between self-employed and employer-employed musicians. We conducted a cross-sectional study of professional musicians. Given the large proportion of musicians who were both self-employed and employer-employed, three groups were compared: self-employed only (self-employed group), employer-employed only (employer-employed group), and both self-employed and employer-employed (both group) musicians. Multivariable regression analyses were conducted. A total of 225 professional musicians were included in the study, 87.9% of whom reported MSSs in the last 12 months. For MSSs that impaired musical activity, the 12-month prevalence was 43.2%. Musicians in the self-employed group reported a significantly higher 7-day prevalence of MSSs compared with those in the employer-employed group. Compared with musicians in the employer-employed group, musicians in the both group reported a higher 12-month prevalence of MSSs that impaired musical activity. A higher proportion of symptomatic musicians in the both group reported seeing a health professional for their MSSs, compared with the employer-employed group. Similarly, symptomatic musicians in the both group reported higher ratings of emotional impact from MSSs, compared with symptomatic musicians in the employer-employed group. The majority of musicians have experienced MSSs. Several significant differences were reported between the three groups of musicians, with musicians in the both group generally reporting poorer MSS outcomes, compared with musicians in the employer-employed group. There are several potential reasons for why musicians who are both self-employed and employer-employed appear to have poorer MSS outcomes, including the stress of balancing multiple demands. Further research is required into the risk factors for MSS outcomes in self-employed musicians, including those who are both self-employed and employer-employed, and interventions should be directed towards self-employed musicians to minimise the MSS burden.

Gut microbiota composition does not associate with toxoplasma infection in rats.

Toxoplasma infection in intermediate host species closely associates with inflammation. This association has led to suggestions that the behavioural changes associated with infection may be indirectly driven by the resulting sustained inflammation rather than a direct behavioural manipulation by the parasite. If this is correct, sustained inflammation in chronically infected rodents should present as widespread differences in the gastrointestinal microbiota due to the dependency between the composition of these microbiota and sustained inflammation. We conducted a randomized controlled experiment in rats that were assigned to a Toxoplasma-treatment, placebo-treatment or negative control group. We euthanised rats during the chronic phase of infection, collected their caecal stool samples and sequenced the V3-V4 region of the 16S rRNA gene to characterize the bacterial community in these samples. Toxoplasma infection did not induce widespread differences in the bacterial community composition of the gastrointestinal tract of rats. Rather, we found sex differences in the bacterial community composition of rats. We conclude that it is unlikely that sustained inflammation is the mechanism driving the highly specific behavioural changes observed in Toxoplasma-positive rats.

Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

Artificial intelligence and machine learning (AI/ML) is becoming increasingly more accessible to biomedical researchers with significant potential to transform biomedicine through optimization of highly-accurate predictive models and enabling better understanding of disease biology. Automated machine learning (AutoML) in particular is positioned to democratize artificial intelligence (AI) by reducing the amount of human input and ML expertise needed. However, successful translation of AI/ML in biomedicine requires moving beyond optimizing only for prediction accuracy and towards establishing reproducible clinical and biological inferences. This is especially challenging for clinical studies on rare disorders where the smaller patient cohorts and corresponding sample size is an obstacle for reproducible modeling results. Here, we present a model-agnostic framework to reinforce AutoML using strategies and tools of explainable and reproducible AI, including novel metrics to assess model reproducibility. The framework enables clinicians to interpret AutoML-generated models for clinical and biological verifiability and consequently integrate domain expertise during model development. We applied the framework towards spinal cord injury prognostication to optimize the intraoperative hemodynamic range during injury-related surgery and additionally identified a strong detrimental relationship between intraoperative hypertension and patient outcome. Furthermore, our analysis captured how evolving clinical practices such as faster time-to-surgery and blood pressure management affect clinical model development. Altogether, we illustrate how expert-augmented AutoML improves inferential reproducibility for biomedical discovery and can ultimately build trust in AI processes towards effective clinical integration.