Publications by authors named "Michael Wood"

305 Publications

Comparison of characteristics and outcomes of patients admitted to hospital with COVID-19 during wave 1 and wave 2 of the current pandemic.

Intern Emerg Med 2021 Oct 12. Epub 2021 Oct 12.

Department of Endocrinology, Ashford and St Peter's Hospitals NHS Foundation Trust, Guildford Road, Chertsey, Surrey, KT16 0PZ, UK.

In this study of patients admitted with COVID-19, we examined differences between the two waves in patient characteristics and outcomes. Data were collected from the first COVID-19 admission to the end of study (01/03/2020-31/03/2021). Data were adjusted for age and sex and presented as odds ratios (OR) with 95% confidence intervals (CI). Among 12,471 admissions, 1452 (11.6%) patients were diagnosed with COVID-19. On admission, the mean (± SD) age of patients with other causes was 68.3 years (± 19.8) and those with COVID-19 in wave 1 was 69.4 years (± 18.0) and wave 2 was 66.2 years (± 18.4). Corresponding ages at discharge were 67.5 years (± 19.7), 63.9 years (± 18.0) and 62.4 years (± 18.0). The highest proportion of total admissions was among the oldest group (≥ 80 years) in wave 1 (35.0%). When compared with patients admitted with other causes, those admitted with COVID-19 in wave 1 and in wave 2 were more frequent in the 40-59 year band: 20.8, 24.6 and 30.0%; consisted of more male patients: 47.5, 57.6 and 58.8%; and a high LACE (Length of stay, Acuity of admission, Comorbidity and Emergency department visits) index (score ≥ 10): 39.4, 61.3 and 50.3%. Compared to wave-2 patients, those admitted in wave 1 had greater risk of death in hospital: OR = 1.58 (1.18-2.12) and within 30 days of discharge: OR = 2.91 (1.40-6.04). Survivors of COVID-19 in wave 1 stayed longer in hospital (median = 6.5 days; interquartile range = 2.9-12.0) as compared to survivors from wave 2 (4.5 days; interquartile range = 1.9-8.7). Patient characteristics differed significantly between the two waves of COVID-19 pandemic. There was an improvement in outcomes in wave 2, including shorter length of stay in hospital and reduction of mortality.
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http://dx.doi.org/10.1007/s11739-021-02842-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505475PMC
October 2021

Comparison of urine fibrinogen and interleukin-6 concentrations between healthy dogs and dogs with risk factors for enterococcal bacteriuria.

Am J Vet Res 2021 Oct;82(10):846-852

Objective: To compare urine concentrations of fibrinogen (uFIB) and interleukin-6 (uIL-6) between dogs with risk factors for enterococcal bacteriuria and healthy dogs.

Sample: Banked urine samples with negative aerobic culture results from 8 dogs with urolithiasis, 9 dogs with anatomic abnormalities of the lower portion of the urinary tract (LUT), 10 dogs with LUT neoplasia, and 21 healthy control dogs.

Procedures: Urine creatinine concentration (uCrea) was determined by an automated biochemical analyzer, and uFIB and uIL-6 were determined by dog-specific ELISAs. The uFIB:uCrea and uIL-6:uCrea ratios were calculated for each sample to normalize intersample differences in urine concentration and were compared among the 4 experimental groups.

Results: Median uFIB:uCrea ratios for dogs with urolithiasis (0.72; interquartile [25th to 75 percentile] range [IQR], 0.46 to 3.48) and LUT neoplasia (6.16; IQR, 3.89 to 12.75), but not for dogs with LUT anatomic abnormalities (0.48; IQR, 0.27 to 0.69), were significantly greater than that for control dogs (0.17; IQR, 0.07 to 0.39). Median uIL-6: uCrea ratios for dogs with urolithiasis (0.48; IQR, 0.18 to 1.61), LUT anatomic abnormalities (0.25; IQR, 0.17 to 0.33), and LUT neoplasia (0.25; IQR, 0.12 to 1.01) were significantly greater than that for control dogs (0.08; IQR, 0.06 to 0.11).

Conclusions And Clinical Relevance: The uFIB and uIL-6 in dogs with risk factors for enterococcal bacteriuria were generally greater than corresponding values in control dogs. Further investigation is necessary to determine the role of fibrinogen in enterococcal colonization of the urinary tract of dogs.
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http://dx.doi.org/10.2460/ajvr.82.10.846DOI Listing
October 2021

Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals.

Elife 2021 09 21;10. Epub 2021 Sep 21.

Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom.

Human herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally integrated HHV-6A/6B (iciHHV-6A/6B) in telomeres. We exploited a hypervariable region of the HHV-6B genome to investigate the relationship between acquired and inherited virus and revealed predominantly maternal transmission of acqHHV-6B in families. Remarkably, we demonstrate that some copies of acqHHV-6B in saliva from healthy adults gained a telomere, indicative of integration and latency, and that the frequency of viral genome excision from telomeres in iciHHV-6B carriers is surprisingly high and varies between tissues. In addition, newly formed short telomeres generated by partial viral genome release are frequently lengthened, particularly in telomerase-expressing pluripotent cells. Consequently, iciHHV-6B carriers are mosaic for different iciHHV-6B structures, including circular extra-chromosomal forms that have the potential to reactivate. Finally, we show transmission of an HHV-6B strain from an iciHHV-6B mother to her non-iciHHV-6B son. Altogether, we demonstrate that iciHHV-6B can readily transition between telomere-integrated and free virus forms.
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http://dx.doi.org/10.7554/eLife.70452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492063PMC
September 2021

An mHealth-Based Intervention for Adolescents With Type 1 Diabetes and Their Parents: Pilot Feasibility and Efficacy Single-Arm Study.

JMIR Mhealth Uhealth 2021 Sep 14;9(9):e23916. Epub 2021 Sep 14.

Pediatric Endocrinology, University of Michigan Medical School, Ann Arbor, MI, United States.

Background: Type 1 diabetes (T1D) affects more than 165,000 individuals younger than 20 years in the United States of America. The transition from parent management to parent-child team management, with the child taking on increased levels of self-care, can be stressful and is associated with a deterioration in self-management behaviors. Therefore, a mobile app intervention, MyT1DHero, was designed to facilitate diabetes-specific positive parent-adolescent communication and improve diabetes-related outcomes. The MyT1DHero intervention links an adolescent with T1D and their parent through 2 separate app interfaces and is designed to promote positive communication regarding T1D management.

Objective: The aim of this pilot study was to determine (1) the initial efficacy of the MyT1DHero intervention in improving diabetes outcomes in adolescents, specifically the hemoglobin A (HbA) levels, diabetes care adherence, and quality of life, and (2) the adolescents' overall satisfaction with this intervention.

Methods: This pilot study included 30 adolescent-parent pairs who used the MyT1DHero app in a 12-week single-arm clinical trial. Participants were recruited from the local pediatric endocrinology subspecialty clinic via snowball sampling. HbA levels, diabetes care adherence, quality of life, family conflict, and satisfaction levels were measured and analyzed using paired sample two-sided t tests and linear regression analyses.

Results: The final analysis included 25 families. The mean age of the adolescents was 12.28 (SD 1.62) years. Half of the participants (13/25) reported a diabetes diagnosis of less than 5 years. After 12 weeks of the intervention, diabetes care adherence significantly improved (before the study: mean 3.87 [SD 0.59]; after the study: mean 4.19 [SD 0.65]; t=-2.52, P=.02, d=0.52) as did quality of life (before the study: mean 4.02 [SD 0.84]; after the study: mean 4.27 [SD 0.73]; t=2.48, P=.01, d=0.32). HbA levels (before the study: mean 8.94 [SD 1.46]; after the study: mean 8.87 [SD 1.29]; t=0.67, P=.51, d=0.04) and family conflict (before the study: mean 2.45 [SD 0.55]; after the study: mean 2.61 [SD 0.45]; t=0.55, P=.14, d=0.32) changed in the hypothesized direction, but the change was not significant. However, higher use of the mobile app was associated with more improvement in HbA levels (F=9.74, P<.005; R=0.33). Overall, the adolescents were satisfied with the app intervention.

Conclusions: In a 12-week pilot study of the mobile app intervention designed to facilitate parent-adolescent communication for improving diabetes outcomes, significant benefits were demonstrated in self-care adherence and quality of life. A randomized controlled trial with a longer intervention is needed to replicate these findings and to determine the stability of the intervention effects.

Trial Registration: ClinicalTrials.gov NCT03436628; https://clinicaltrials.gov/ct2/show/NCT03436628.
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http://dx.doi.org/10.2196/23916DOI Listing
September 2021

COVID-19 and autoinflammatory diseases: prevalence and outcomes of infection and early experience of vaccination in patients on biologics.

Rheumatol Adv Pract 2021 23;5(2):rkab043. Epub 2021 Aug 23.

CAPS and Autoinflammatory Diseases Treatment Service, National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital.

Objectives: The systemic autoinflammatory diseases are rare conditions; to date, data on coronavirus disease 2019 (COVID-19) infection and vaccination safety are scarce. Agents targeting innate immune pathways have transformed the management of affected patients, and their outcomes are of wider interest given the role of inflammation in both viral clearance and severe COVID-19 disease. We surveyed patients with systemic autoinflammatory disease on biologic therapy to determine the prevalence and outcomes of COVID-19 infection and to gather early safety data on vaccination.

Methods: Electronic medical records of 248 patients with systemic autoinflammatory disease on biologic therapy at a national centre were reviewed. Patients were then surveyed in clinic or using a Web-based survey.

Results: In the cohort of 248 patients, no deaths were recorded. One hundred and seventy-five survey responses were received. Among the respondents, 27 reported suspected COVID-19 infection, of which 14 were confirmed by testing (8.0%). Two patients required hospital admission owing to dehydration. No patient required respiratory support or intensive care. One hundred and thirty-eight doses of COVID-19 vaccine had been administered to 130 patients. Side effects were reported after 71 of 138 (51.4%) administrations and were consistent with a flare of the underlying disease in 26 of 138 (18.8%) instances. No serious adverse events or hospital admissions were reported after vaccination.

Conclusion: These data, including the largest published series of patients on anti-IL-1/6 biologics to receive any adenoviral vector or messenger RNA vaccine, show no serious early concerns regarding vaccination and will provide an urgently needed resource to inform decision-making of these patients and their clinicians.
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http://dx.doi.org/10.1093/rap/rkab043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397842PMC
August 2021

Fungal microbiomes are determined by host phylogeny and exhibit widespread associations with the bacterial microbiome.

Proc Biol Sci 2021 08 18;288(1957):20210552. Epub 2021 Aug 18.

School of Science and Computing, Waterford Institute of Technology, Ireland.

Interactions between hosts and their resident microbial communities are a fundamental component of fitness for both agents. Though recent research has highlighted the importance of interactions between animals and their bacterial communities, comparative evidence for fungi is lacking, especially in natural populations. Using data from 49 species, we present novel evidence of strong covariation between fungal and bacterial communities across the host phylogeny, indicative of recruitment by hosts for specific suites of microbes. Using co-occurrence networks, we demonstrate marked variation across host taxonomy in patterns of covariation between bacterial and fungal abundances. Host phylogeny drives differences in the overall richness of bacterial and fungal communities, but the effect of diet on richness was only evident in the mammalian gut microbiome. Sample type, tissue storage and DNA extraction method also affected bacterial and fungal community composition, and future studies would benefit from standardized approaches to sample processing. Collectively these data indicate fungal microbiomes may play a key role in host fitness and suggest an urgent need to study multiple agents of the animal microbiome to accurately determine the strength and ecological significance of host-microbe interactions.
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http://dx.doi.org/10.1098/rspb.2021.0552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370808PMC
August 2021

Survival from Maternal Cardiac Arrest Complicating Coronavirus Disease 2019.

Case Rep Obstet Gynecol 2021 19;2021:3762198. Epub 2021 Jul 19.

Department of Medicine, Shannon Medical Center, San Angelo, Texas, USA.

Introduction: Coronavirus disease 2019 (COVID-19) has been linked to significant cardiovascular complications such as cardiac arrest, which are associated with a poor prognosis in adults. Little is known about the cardiac complications, specifically cardiac arrest, of COVID-19 during pregnancy and postpartum periods.

Case: We present a case of survival and full neurological recovery after maternal cardiac arrest associated with COVID-19 in a postpartum female. Her postpartum course was also associated with seizures attributed to posterior reversible encephalopathy syndrome. After 19 days in the hospital, she was discharged home neurologically intact.

Conclusion: More information is needed to determine the range of short- and long-term cardiac complications that may be associated with COVID-19 during pregnancy and postpartum. Additionally, pregnant patients with COVID-19 may be more likely to survive cardiac arrest compared to the general population.
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http://dx.doi.org/10.1155/2021/3762198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292066PMC
July 2021

COVID-19-associated ischaemic stroke despite use of anticoagulation.

BMJ Case Rep 2021 Jul 29;14(7). Epub 2021 Jul 29.

Stroke Unit, Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.

A 64-year-old female nurse was admitted to hospital following fever, cough, shortness of breath and low blood pressure. She tested positive for COVID-19 and was treated on a high-dependency unit and prescribed enoxaparin, a prophylactic anticoagulant. Eight days later, she suffered a left middle cerebral artery ischaemic stroke. Over the next 2 weeks, her condition fluctuated, eventually leading to her death. We report her case from clinical history to investigations and outcomes, and explore the potential link between coronavirus, the use of anticoagulation and ischaemic stroke.
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http://dx.doi.org/10.1136/bcr-2021-243741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323371PMC
July 2021

Transpalatal reconstruction and stenting for treatment of choanal atresia and nasopharyngeal stenosis in a dog.

J Am Vet Med Assoc 2021 Jul;259(2):190-196

Case Description: A 3-year-old 17.5-kg (38.5-lb) mixed-breed dog was referred for evaluation because of nasal discharge, sneezing, and signs of nasal congestion of approximately 9 months' duration. A diagnosis of nasopharyngeal stenosis (NPS) was made prior to referral.

Clinical Findings: Sneezing, bilateral mucopurulent nasal discharge, reduced nasal airflow, stertor, and increased inspiratory effort were noted on physical examination. Results of serum biochemical analysis were within respective reference ranges. Review of CT images of the skull revealed findings consistent with severe bilateral partial osseous choanal atresia and NPS. Retrograde rhinoscopy confirmed membranous NPS.

Treatment And Outcome: A ventral rhinotomy was performed; communication between the pharynx and nasal passageway was reestablished by surgical debridement of the caudal border of the palatine bone and vomerine crest and groove, followed by dissection of the membranous NPS and reconstruction of the caudal part of the nasopharynx. A covered nasopharyngeal stent was placed in the newly established nasopharynx. The dog recovered uneventfully but was presented 3 weeks later with recurrent signs; diagnostic findings were consistent with stenosis rostral to the stent. The stenosis was treated with balloon dilation, and a second covered stent was placed rostral to and overlapping the first stent, spanning the stenotic region. Eleven months after this procedure, the dog was doing well.

Clinical Relevance: Results for this patient suggested that ventral rhinotomy and covered nasopharyngeal stent placement can be used successfully for the management of osseous choanal atresia in dogs; however, careful attention to preoperative planning and potential complications is necessary.
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http://dx.doi.org/10.2460/javma.259.2.190DOI Listing
July 2021

Retreat of Humboldt Gletscher, North Greenland, Driven by Undercutting From a Warmer Ocean.

Geophys Res Lett 2021 Mar 24;48(6):e2020GL091342. Epub 2021 Mar 24.

School of Marine Science and Policy University of Delaware Newark DE USA.

Humboldt Gletscher is a 100-km wide, slow-moving glacier in north Greenland which holds a 19-cm global sea level equivalent. Humboldt has been the fourth largest contributor to sea level rise since 1972 but the cause of its mass loss has not been elucidated. Multi-beam echo sounding data collected in 2019 indicate a seabed 200 m deeper than previously known. Conductivity temperature depth data reveal the presence of warm water of Atlantic origin at 0°C at the glacier front and a warming of the ocean waters by 0.9 ± 0.1°C since 1962. Using an ocean model, we reconstruct grounded ice undercutting by the ocean, combine it with calculated retreat caused by ice thinning to floatation, and are able to fully explain the observed retreat. Two thirds of the retreat are caused by undercutting of grounded ice, which is a physical process not included in most ice sheet models.
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http://dx.doi.org/10.1029/2020GL091342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243930PMC
March 2021

Continuous positive airway pressure therapy reduces the levels of catecholamines and blood pressure in pseudophaeochromocytoma with coexisting obstructive sleep apnoea.

JRSM Cardiovasc Dis 2021 Jan-Dec;10:2048004021992191. Epub 2021 Mar 17.

Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, Surrey, UK.

Background: Stress from obstructive sleep apnoea (OSA) stimulates catecholamine release and consequently can exacerbate hypertension, even in the absence of a catecholamine-producing tumour (phaeochromocytoma). As such, a positive screening test for suspected phaeochromocytoma may be misleading. There exists only a handful case reports, and no controlled trials, how continuous positive airway pressure (CPAP) to treat OSA influences catecholamine levels. We examined changes to levels of urinary catecholamine and blood pressure in response to CPAP treatment.

Methods: We conducted a meta-analysis of data aggregated from published case reports of individual patient data up to April 2020. The quality of the reports was evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool.

Results: A total of 13 cases (seven men and six women) from seven reports met our search criteria. Patients had mean age of 49.1 years (range = 36-62) and body mass index of 37.4 kg/m (range = 27-56). Most had moderate to severe OSA with CPAP treatment. Nine cases had 24-hour urinary noradrenaline assessment before and after CPAP treatment. CPAP treatment led to a 21% reduction (104 nmol/24-hours, 95% credible interval =59 to 148) in 24-hour urinary noradrenaline to within reference ranges, and 25% reduction (from 131 to 100 mmHg) in mean arterial pressure. The risk of overall bias evaluated by the ROBINS-I tool was found to be low in the majority of reports.

Conclusions: Investigations of patients suspected of phaeochromocytoma, particularly obese individuals, should exclude OSA and treat this condition if present before performing screening tests to assess for catecholamine levels.
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http://dx.doi.org/10.1177/2048004021992191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217809PMC
March 2021

Principal Components Analysis Using Data Collected From Healthy Individuals on Two Robotic Assessment Platforms Yields Similar Behavioral Patterns.

Front Hum Neurosci 2021 6;15:652201. Epub 2021 May 6.

Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.

Background: Kinarm Standard Tests (KSTs) is a suite of upper limb tasks to assess sensory, motor, and cognitive functions, which produces granular performance data that reflect spatial and temporal aspects of behavior (>100 variables per individual). We have previously used principal component analysis (PCA) to reduce the dimensionality of multivariate data using the Kinarm End-Point Lab (EP). Here, we performed PCA using data from the Kinarm Exoskeleton Lab (EXO), and determined agreement of PCA results across EP and EXO platforms in healthy participants. We additionally examined whether further dimensionality reduction was possible by using PCA across behavioral tasks.

Methods: Healthy participants were assessed using the Kinarm EXO ( = 469) and EP ( = 170-200). Four behavioral tasks (six assessments in total) were performed that quantified arm sensory and motor function, including position sense [Arm Position Matching (APM)] and three motor tasks [Visually Guided Reaching (VGR), Object Hit (OH), and Object Hit and Avoid (OHA)]. The number of components to include per task was determined from scree plots and parallel analysis, and rotation type (orthogonal vs. oblique) was decided on a per-task basis. To assess agreement, we compared principal components (PCs) across platforms using distance correlation. We additionally considered inter-task interactions in EXO data by performing PCA across all six behavioral assessments.

Results: By applying PCA on a per task basis to data collected using the EXO, the number of behavioral parameters were substantially reduced by 58-75% while accounting for 76-87% of the variance. These results compared well to the EP analysis, and we found good-to-excellent agreement values (0.75-0.99) between PCs from the EXO and those from the EP. Finally, we were able to reduce the dimensionality of the EXO data across tasks down to 16 components out of a total of 76 behavioral parameters, which represents a reduction of 79% while accounting for 73% of the total variance.

Conclusion: PCA of Kinarm robotic assessment appears to capture similar relationships between kinematic features in healthy individuals and is agnostic to the robotic platform used for collection. Further work is needed to investigate the use of PCA-based data reduction for the characterization of neurological deficits in clinical populations.
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http://dx.doi.org/10.3389/fnhum.2021.652201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134538PMC
May 2021

The Tuning of LIPSS Wettability during Laser Machining and through Post-Processing.

Nanomaterials (Basel) 2021 Apr 10;11(4). Epub 2021 Apr 10.

Department of Chemical Engineering, McGill University, Montréal, QC H3A 0C5, Canada.

In this work, we investigate the fabrication of stainless-steel substrates decorated with laser-induced periodic surface structures (LIPSS) of both hydrophilic and hydrophobic wettability through different post-processing manipulation. In carrying out these experiments, we have found that while a CO-rich atmosphere during irradiation does not affect final wettability, residence in such an atmosphere after irradiation does indeed increase hydrophobicity. Contrarily, residence in a boiling water bath will instead lead to a hydrophilic surface. Further, our experiments show the importance of removing non-sintered nanoparticles and agglomerates after laser micromachining. If they are not removed, we demonstrate that the nanoparticle agglomerates themselves become hydrophobic, creating a Cassie air-trapping layer on the surface which presents with water contact angles of 180°. However, such a surface lacks robustness; the particles are removed with the contacting water. What is left behind are LIPSS which are integral to the surface and have largely been blocked from reacting with the surrounding atmosphere. The actual surface presents with a water contact angle of approximately 80°. Finally, we show that chemical reactions on these metallic surfaces decorated with only LIPSS are comparatively slower than the reactions on metals irradiated to have hierarchical roughness. This is shown to be an important consideration to achieve the highest degree of hydro-philicity/phobicity possible. For example, repeated contact with water from goniometric measurements over the first 30 days following laser micromachining is shown to reduce the ultimate wettability of the surface to approximately 65°, compared to 135° when the surface is left undisturbed for 30 days.
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http://dx.doi.org/10.3390/nano11040973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069829PMC
April 2021

Impacts of radiation exposure on the bacterial and fungal microbiome of small mammals in the Chernobyl Exclusion Zone.

J Anim Ecol 2021 Sep 21;90(9):2172-2187. Epub 2021 May 21.

School of Science, Engineering and Environment, University of Salford, Salford, UK.

Environmental impacts of the 1986 Chernobyl Nuclear Power Plant accident are much debated, but the effects of radiation on host microbiomes have received little attention to date. We present the first analysis of small mammal gut microbiomes from the Chernobyl Exclusion Zone in relation to total absorbed dose rate, including both caecum and faeces samples. We provide novel evidence that host species determines fungal community composition, and that associations between microbiome (both bacterial and fungal) communities and radiation exposure vary between host species. Using ambient versus total weighted absorbed dose rates in analyses produced different results, with the latter more robust for interpreting microbiome changes at the individual level. We found considerable variation between results for faecal and gut samples of bank voles, suggesting faecal samples are not an accurate indicator of gut composition. Associations between radiation exposure and microbiome composition of gut samples were not robust against geographical variation, although we identified families of bacteria (Lachnospiraceae and Muribaculaceae) and fungi (Steccherinaceae and Strophariaceae) in the guts of bank voles that may serve as biomarkers of radiation exposure. Further studies considering a range of small mammal species are needed to establish the robustness of these potential biomarkers.
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http://dx.doi.org/10.1111/1365-2656.13507DOI Listing
September 2021

Wildfires in the Chornobyl exclusion zone-Risks and consequences.

Integr Environ Assess Manag 2021 Nov 13;17(6):1141-1150. Epub 2021 May 13.

School of Science, Engineering & Environment, University of Salford, Manchester, UK.

Following the 1986 Chornobyl accident, an area approaching 5000 km surrounding the nuclear plant was abandoned, creating the Chornobyl exclusion zone (CEZ). Although this area likely contains the most radioactive terrestrial ecosystem on earth, the absence of humans and associated activities for nearly 35 years since the accident has resulted in increases in wildlife numbers. Both the Belarussian and Ukrainian components of the CEZ are now designated as nature reserves; together they form one of Europe's largest protected areas and have been described as an iconic example of rewilding. Forests and former agricultural land (now scrub) dominate the CEZ and wildfires are an annual event. In April 2020, the CEZ suffered its most widespread fires to date when greater than 800 km of the 2600 km Ukrainian portion of the CEZ was burnt. Large-scale fires in the CEZ have implications for wildlife, as they do elsewhere, but they also pose additional radioecological and radiological protection questions. We discuss the implications of wildfires in the CEZ, considering effects on wildlife and changes in radionuclide mobility. We also demonstrate that the risk to firefighters and the wider public from the inhalation of radionuclides in smoke resulting from fires in the CEZ is likely to be low. However, further experimental and modeling work to evaluate potential doses to firefighters from inhaled radioactive particles would be valuable, not least for reassurance purposes. Integr Environ Assess Manag 2021;17:1141-1150 © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
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http://dx.doi.org/10.1002/ieam.4424DOI Listing
November 2021

The Use of Near-Infrared Spectroscopy and/or Transcranial Doppler as Non-Invasive Markers of Cerebral Perfusion in Adult Sepsis Patients With Delirium: A Systematic Review.

J Intensive Care Med 2021 Mar 9:885066621997090. Epub 2021 Mar 9.

Department of Anesthesiology, Pharmacology and Therapeutics, 8166University of British Columbia, Vancouver, British Columbia, Canada.

Background: Several studies have previously reported the presence of altered cerebral perfusion during sepsis. However, the role of non-invasive neuromonitoring, and the impact of altered cerebral perfusion, in sepsis patients with delirium remains unclear.

Methods: We performed a systematic review of studies that used near-infrared spectroscopy (NIRS) and/or transcranial Doppler (TCD) to assess adults (≥18 years) with sepsis and delirium. From study inception to July 28, 2020, we searched the following databases: Ovid MedLine, Embase, Cochrane Library, and Web of Science.

Results: Of 1546 articles identified, 10 met our inclusion criteria. Although NIRS-derived regional cerebral oxygenation was consistently lower, this difference was only statistically significant in one study. TCD-derived cerebral blood flow velocity was inconsistent across studies. Importantly, both impaired cerebral autoregulation during sepsis and increased cerebrovascular resistance were associated with delirium during sepsis. However, the heterogeneity in NIRS and TCD devices, duration of recording (from 10 seconds to 72 hours), and delirium assessment methods (e.g., electronic medical records, confusion assessment method for the intensive care unit), precluded meta-analysis.

Conclusion: The available literature demonstrates that cerebral perfusion disturbances may be associated with delirium in sepsis. However, future investigations will require consistent definitions of delirium, delirium assessment training, harmonized NIRS and TCD assessments (e.g., consistent measurement site and length of recording), as well as the quantification of secondary and tertiary variables (i.e., Cox, Mxa, MAP), in order to fully assess the relationship between cerebral perfusion and delirium in patients with sepsis.
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http://dx.doi.org/10.1177/0885066621997090DOI Listing
March 2021

The complete mitochondrial genome of the Indian leafwing butterfly (insecta: Lepidoptera: Nymphalidae).

Mitochondrial DNA B Resour 2021 Jan 27;6(1):274-277. Epub 2021 Jan 27.

Department of Biological Sciences, University of Manitoba, Winnipeg, Canada.

The Indian leafwing butterfly (Horsfield, 1829) (Nymphalidae) is an Asian forest-dwelling, leaf-mimic. Genome skimming by Illumina sequencing permitted assembly of a complete circular mitogenome of 15,200 bp from consisting of 79.5% AT nucleotides, 22 tRNAs, 13 protein-coding genes, two rRNAs and a control region in the typical butterfly gene order. features an atypical CGA start codon, while , , and exhibit incomplete stop codons completed by 3' A residues added to the mRNA. Phylogenetic reconstruction places within the monophyletic genus , sister to in the subfamily Nymphalinae. These data support the monophyly of tribe Kallimini and contribute to the evolutionary systematics of the Nymphalidae.
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http://dx.doi.org/10.1080/23802359.2020.1862000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850329PMC
January 2021

Ocean forcing drives glacier retreat in Greenland.

Sci Adv 2021 Jan 1;7(1). Epub 2021 Jan 1.

Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA.

The retreat and acceleration of Greenland glaciers since the mid-1990s have been attributed to the enhanced intrusion of warm Atlantic Waters (AW) into fjords, but this assertion has not been quantitatively tested on a Greenland-wide basis or included in models. Here, we investigate how AW influenced retreat at 226 marine-terminating glaciers using ocean modeling, remote sensing, and in situ observations. We identify 74 glaciers in deep fjords with AW controlling 49% of the mass loss that retreated when warming increased undercutting by 48%. Conversely, 27 glaciers calving on shallow ridges and 24 in cold, shallow waters retreated little, contributing 15% of the loss, while 10 glaciers retreated substantially following the collapse of several ice shelves. The retreat mechanisms remain undiagnosed at 87 glaciers without ocean and bathymetry data, which controlled 19% of the loss. Ice sheet projections that exclude ocean-induced undercutting may underestimate mass loss by at least a factor of 2.
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http://dx.doi.org/10.1126/sciadv.aba7282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775757PMC
January 2021

Ocean melting of the Zachariae Isstrøm and Nioghalvfjerdsfjorden glaciers, northeast Greenland.

Proc Natl Acad Sci U S A 2021 01;118(2)

National Space Institute, Geodesy and Earth Observation, Technical University of Denmark, 2800 Lyngby, Denmark.

Zachariae Isstrøm (ZI) and Nioghalvfjerdsfjorden (79N) are marine-terminating glaciers in northeast Greenland that hold an ice volume equivalent to a 1.1-m global sea level rise. ZI lost its floating ice shelf, sped up, retreated at 650 m/y, and experienced a 5-gigaton/y mass loss. Glacier 79N has been more stable despite its exposure to the same climate forcing. We analyze the impact of ocean thermal forcing on the glaciers. A three-dimensional inversion of airborne gravity data reveals an 800-m-deep, broad channel that allows subsurface, warm, Atlantic Intermediate Water (AIW) (+1.[Formula: see text]C) to reach the front of ZI via two sills at 350-m depth. Subsurface ocean temperature in that channel has warmed by 1.3[Formula: see text]C since 1979. Using an ocean model, we calculate a rate of ice removal at the grounding line by the ocean that increased from 108 m/y to 185 m/y in 1979-2019. Observed ice thinning caused a retreat of its flotation line to increase from 105 m/y to 217 m/y, for a combined grounding line retreat of 13 km in 41 y that matches independent observations within 14%. In contrast, the limited access of AIW to 79N via a narrower passage yields lower grounded ice removal (53 m/y to 99 m/y) and thinning-induced retreat (27 m/y to 50 m/y) for a combined retreat of 4.4 km, also within 12% of observations. Ocean-induced removal of ice at the grounding line, modulated by bathymetric barriers, is therefore a main driver of ice sheet retreat, but it is not incorporated in most ice sheet models.
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http://dx.doi.org/10.1073/pnas.2015483118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812800PMC
January 2021

Near-Infrared Spectroscopy to Assess Cerebral Autoregulation and Optimal Mean Arterial Pressure in Patients With Hypoxic-Ischemic Brain Injury: A Prospective Multicenter Feasibility Study.

Crit Care Explor 2020 Oct 25;2(10):e0217. Epub 2020 Sep 25.

Division of Cardiology, Department of Medicine, University of Toronto, Toronto, ON, Canada.

We provide preliminary multicenter data to suggest that recruitment and collection of physiologic data necessary to quantify cerebral autoregulation and individualized blood pressure targets are feasible in postcardiac arrest patients. We evaluated the feasibility of a multicenter protocol to enroll patients across centers, as well as collect continuous recording (≥ 80% of monitoring time) of regional cerebral oxygenation and mean arterial pressure, which is required to quantify cerebral autoregulation, using the cerebral oximetry index, and individualized optimal mean arterial pressure thresholds. Additionally, we conducted an exploratory analysis to assess if an increased percentage of monitoring time where mean arterial pressure was greater than or equal to 5 mm Hg below optimal mean arterial pressure, percentage of monitoring time with dysfunctional cerebral autoregulation (i.e., cerebral oximetry index ≥ 0.3), and time to return of spontaneous circulation were associated with an unfavorable neurologic outcome (i.e., 6-mo Cerebral Performance Category score ≥ 3).

Design Setting And Patients: A prospective multicenter cohort study was conducted in ICUs in three teaching hospitals across Canada. Patients (≥ 16 yr old) were included if their cardiac arrest occurred within the previous 36 hours, they had greater than or equal to 20 consecutive minutes of spontaneous circulation following resuscitation, and they had a post-resuscitation Glasgow Coma Scale of less than or equal to 8.

Measurements And Main Results: Recruitment rates were calculated across sites, and patients underwent continuous regional cerebral oxygenation monitoring using near-infrared spectroscopy, as well as invasive blood pressure monitoring. Exploratory multivariable logistic regression was performed. Although it was feasible to recruit patients across multiple centers, there was variability in the recruitment rates. Physiologic data were captured in 86.2% of the total monitoring time and the median monitoring time was 47.5 hours (interquartile interval, 29.4-65.0 hr) across 59 patients. Specifically, 88% of mean arterial pressure and 96% of bilateral frontal regional cerebral oxygenation data were acquired, and 90% of cerebral oximetry index and 70% of optimal mean arterial pressure values were quantified. However, there was substantial variation in the amount of data captured among individuals. Time to return of spontaneous circulation was associated with an increased odds of an unfavorable neurologic outcome.

Conclusions And Relevance: We demonstrated feasibility to recruit and collect high frequency physiologic data in patients after cardiac arrest. Future investigations will need to systematically document the reasons for data attrition, as well as how these methodological complications were resolved. Due to underpowered analyses and the inability to control for potential confounds, further studies are needed to explore the association between cerebral autoregulatory capacity and individualized mean arterial pressure thresholds with neurologic outcomes.
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http://dx.doi.org/10.1097/CCE.0000000000000217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523861PMC
October 2020

Risk factors for enterococcal bacteriuria in dogs: A retrospective study.

J Vet Intern Med 2020 Nov 2;34(6):2447-2453. Epub 2020 Oct 2.

Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Background: In humans, Enterococcus spp. urinary tract infections (UTI) are commonly associated with urinary catheter-induced urothelial inflammation but this is not the case in dogs.

Hypothesis/objectives: To identify risk factors predisposing dogs to enterococcal bacteriuria.

Animals: Seventy dogs with Enterococcus spp. bacteriuria (case) and 70 dogs with Enterococcus coli bacteriuria (control).

Methods: A single center retrospective case-control study with subjects and controls identified by a medical records search for Enterococcus spp. (subject) or E coli (control) bacteriuria from January 1, 2014 to December 31, 2017. Cases and controls were balanced with respect to average age and weight. Binary logistic regression was used to estimate and test whether the odds of having Enterococcus spp. bacteriuria (instead of E coli) were associated with the presence of any given characteristic.

Results: A history of recurrent bacteriuria was significantly more common in Enterococcus spp. cases than in E coli controls (odds ratio [OR]: 2.07; 95% confidence interval [CI]: 1.04-4.16, P = .04). Comorbidities associated with the presence of Enterococcus spp. bacteriuria included lower urinary tract (LUT) anatomic abnormalities (OR: 2.94; 95% CI: 1.17-8.10, P = .02), urolithiasis (P = .01), and the presence of LUT neoplasia (P = .04). Small frequencies (n = 12 and n = 6, respectively) compromise our ability to precisely estimate the genuine OR for the latter 2 characteristics.

Conclusions And Clinical Importance: If the identified risk factors promote Enterococcus spp. colonization in dogs via induced LUT inflammation similar to people then Enterococcus spp. bacteriuria could be a sentinel for underlying LUT inflammation.
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http://dx.doi.org/10.1111/jvim.15916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694861PMC
November 2020

Direct-write orientation of charge-transfer liquid crystals enables polarization-based coding and encryption.

Sci Rep 2020 Sep 18;10(1):15352. Epub 2020 Sep 18.

Department of Chemistry, Denison University, Granville, OH, 43023, USA.

Optical polarizers encompass a class of anisotropic materials that pass-through discrete orientations of light and are found in wide-ranging technologies, from windows and glasses to cameras, digital displays and photonic devices. The wire-grids, ordered surfaces, and aligned nanomaterials used to make polarized films cannot be easily reconfigured once aligned, limiting their use to stationary cross-polarizers in, for example, liquid crystal displays. Here we describe a supramolecular material set and patterning approach where the polarization angle in stand-alone films can be precisely defined at the single pixel level and reconfigured following initial alignment. This capability enables new routes for non-binary information storage, retrieval, and intrinsic encryption, and it suggests future technologies such as photonic chips that can be reconfigured using non-contact patterning.
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http://dx.doi.org/10.1038/s41598-020-72037-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501303PMC
September 2020

Adding vitamin C to hydrocortisone lacks benefit in septic shock: a historical cohort study.

Can J Anaesth 2020 Dec 16;67(12):1798-1805. Epub 2020 Sep 16.

Division of Critical Care Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.

Purpose: Sepsis has high incidence and mortality rates, particularly in the intensive care unit (ICU). Corticosteroids may improve outcomes, and vitamin C may add benefit. We aimed to assess whether vitamin C and corticosteroids improved outcomes compared with corticosteroids alone.

Methods: This historical cohort study (11 December 2016 to 21 February 2018) was conducted in the ICU of a quaternary referral hospital. Patients with an ICU admission diagnosis of sepsis or septic shock who received vitamin C and hydrocortisone within 72 hr were compared with those who received only hydrocortisone. All patients received standard sepsis care including source control, antibiotics, and fluid resuscitation. Most patients received thiamine as standard ICU care. The primary outcome was hospital mortality. Secondary outcomes included ICU mortality, ventilator-free days, vasopressor-free days, dialysis use, and duration of ICU admission.

Results: One hundred and forty-four patients were included in the study. The mean (standard deviation [SD]) age was 64 (15) yr; 39% were female; and the mean (SD) Acute Physiology And Chronic Health Evaluation IV score was 89 (30). Eighty-eight patients did not receive vitamin C and 52 received vitamin C. There was no observed difference in hospital mortality between the non-vitamin C (36%) and vitamin C (39%) groups (adjusted odds ratio for hospital death, 0.52; 95% confidence interval, 0.20 to 1.34; P = 0.18). There were no statistically significant differences in any secondary outcomes.

Conclusion: In this small observational study of ICU patients with septic shock, the addition of vitamin C to hydrocortisone therapy did significantly affect hospital mortality or other measures of mortality or organ dysfunction.
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http://dx.doi.org/10.1007/s12630-020-01814-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493833PMC
December 2020

Clustering in a newly forming social network by subjective perceptions of loneliness.

J Am Coll Health 2020 Sep 2:1-6. Epub 2020 Sep 2.

Department of Sociology, University of Notre Dame, Notre Dame, Indiana, USA.

Objectives: To determine whether first-year college students cluster in networks based on subjective perceptions of loneliness. 492 first-year Notre Dame students completed surveys across two semesters and provided communication data used to reconstruct their social networks. Subjective perceptions of loneliness are measured using the Social and Emotional Loneliness Scale for Adults (SELSA). Correlations between an individual's loneliness and the average loneliness of their alters are compared to associations in random networks created using a rewiring algorithm to determine statistical significance. During their first semester, students are more likely than chance to form ties with other students with similar levels of family and romantic loneliness. In their second semester, students cluster on romantic loneliness but not on family or social loneliness. Students are more likely than chance to form ties with people with similar self-perceived levels of loneliness, but only for certain types of loneliness and during certain periods.
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http://dx.doi.org/10.1080/07448481.2020.1806852DOI Listing
September 2020

Delirium, Cerebral Perfusion, and High-Frequency Vital-Sign Monitoring in the Critically Ill. The CONFOCAL-2 Feasibility Study.

Ann Am Thorac Soc 2021 01;18(1):112-121

Centre for Neuroscience Studies.

Studies suggest that reduced cerebral perfusion may contribute to delirium development in the intensive care unit (ICU). However, evidence is limited because of factors including small sample size and limited inclusion of covariates. To assess the feasibility of a multicenter prospective observational study using a multimodal data collection platform. Feasibility was assessed by enrollment, data-capture, and follow-up rates. The full study will aim to assess the association between noninvasively derived surrogate markers of cerebral perfusion, delirium development, and long-term cognitive outcomes in critically ill patients. Adult patients in the ICU were enrolled if they had shock and/or respiratory failure requiring invasive mechanical ventilation for >24 hours. For the first 72 hours, a near-infrared spectroscopic sensor was placed on the forehead to continuously monitor regional cerebral oxygenation (rSo) and high-frequency (1 Hz) vital signs were concurrently captured via an arterial line. Cerebral perfusion was estimated using three variables, including mean rSo, duration of disturbed autoregulation, and time/magnitude away from optimal mean arterial pressure (MAP). Patients were screened for delirium in the ICU and ward daily for up to 30 days. Cognitive function was assessed 3 and 12 months after ICU admission to identify cognitive impairment. Fifty-nine patients were enrolled across four sites in 1 year. Data-capture rates varied across modalities but exceeded 80% for rSo, blood gas, and delirium data capture. Vital-sign capture and 3-month follow-up rates were lower at 53% and 55%, respectively. Eighty-three percent (49 of 59) of patients experienced delirium, with a median severity of 0.56 in the ICU. Mean physiological (±standard deviation) values were: rSo (70.4% ± 7.0%), heart rate (83.9 ± 16.45 beats/min), MAP (76.4 ± 12.8 mm Hg), peripheral oxygenation saturation (96.5% ± 2.1%), proportion of recording time spent with disturbed autoregulation (10.1% ± 7.3%) and proportion of area under the curve outside optimal MAP (39.6% ± 22.4%). Thirty-two (54%) individuals had cerebral autoregulation curves where a targeted optimal MAP was identified. Barriers to data collection included missing vital-sign data and low follow-up rates. Given our current protocol, a multicenter study examining the association between cerebral oxygenation, delirium, and long-term cognitive impairment is not feasible. However, by performing an early assessment of feasibility, we identified strategies to increase capture rates to ensure success as the study begins the next phase of study recruitment.Clinical trial registered with clinicaltrials.gov (NCT03141619).
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http://dx.doi.org/10.1513/AnnalsATS.202002-093OCDOI Listing
January 2021

Variability and Standardization of Quantitative Imaging.

Authors:
Michael L Wood

Invest Radiol 2020 09;55(9):617-618

From North York General Hospital, and Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1097/RLI.0000000000000667DOI Listing
September 2020

An immunohistochemical prostate cell identification key indicates that aging shifts procollagen 1A1 production from myofibroblasts to fibroblasts in dogs prone to prostate-related urinary dysfunction.

PLoS One 2020 29;15(7):e0232564. Epub 2020 Jul 29.

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, University of Wisconsin- Madison, Madison, Wisconsin, United States of America.

Background: The identity and spatial distribution of prostatic cell types has been determined in humans but not in dogs, even though aging- and prostate-related voiding disorders are common in both species and mechanistic factors, such as prostatic collagen accumulation, appear to be shared between species. In this publication we characterize the regional distribution of prostatic cell types in the young intact dog to enable comparisons with human and mice and we examine how the cellular source of procollagen 1A1 changes with age in intact male dogs.

Methods: A multichotomous decision tree involving sequential immunohistochemical stains was validated for use in dog and used to identify specific prostatic cell types and determine their distribution in the capsule, peripheral, periurethral and urethral regions of the young intact canine prostate. Prostatic cells identified using this technique include perivascular smooth muscle cells, pericytes, endothelial cells, luminal, intermediate, and basal epithelial cells, neuroendocrine cells, myofibroblasts, fibroblasts, fibrocytes, and other hematolymphoid cells. To enhance rigor and transparency, all high resolution images (representative images shown in the figures and biological replicates) are available through the GUDMAP database at https://doi.org/10.25548/16-WMM4.

Results: The prostatic peripheral region harbors the largest proportion of epithelial cells. Aging does not change the density of hematolymphoid cells, fibroblasts, and myofibroblasts in the peripheral region or in the fibromuscular capsule, regions where we previously observed aging- and androgen-mediated increases in prostatic collagen abundance Instead, we observed aging-related changes the procollagen 1A1 positive prostatic cell identity from a myofibroblast to a fibroblast.

Conclusions: Hematolymphoid cells and myofibroblasts are often identified as sources of collagen in tissues prone to aging-related fibrosis. We show that these are not the likely sources of pathological collagen synthesis in older intact male dogs. Instead, we identify an aging-related shift in the prostatic cell type producing procollagen 1A1 that will help direct development of cell type and prostate appropriate therapeutics for collagen accumulation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232564PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390344PMC
September 2020

From tangled banks to toxic bunnies; a reflection on the issues involved in developing an ecosystem approach for environmental radiation protection.

Int J Radiat Biol 2020 Jul 21:1-16. Epub 2020 Jul 21.

School of Science, Engineering & Environment, University of Salford, Salford, UK.

The objective of this paper is to present the results of discussions at a workshop held as part of the International Congress of Radiation Research (Environmental Health stream) in Manchester UK, 2019. The main objective of the workshop was to provide a platform for radioecologists to engage with radiobiologists to address major questions around developing an Ecosystem approach in radioecology and radiation protection of the environment. The aim was to establish a critical framework to guide research that would permit integration of a pan-ecosystem approach into radiation protection guidelines and regulation for the environment. The conclusions were that the interaction between radioecologists and radiobiologists is useful in particular in addressing field versus laboratory issues where there are issues and challenges in designing good field experiments and a need to cross validate field data against laboratory data and vice versa. Other main conclusions were that there is a need to appreciate wider issues in ecology to design good approaches for an ecosystems approach in radioecology and that with the capture of 'Big Data', novel tools such as machine learning can now be applied to help with the complex issues involved in developing an ecosystem approach.
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http://dx.doi.org/10.1080/09553002.2020.1793022DOI Listing
July 2020

The International Bathymetric Chart of the Arctic Ocean Version 4.0.

Sci Data 2020 07 9;7(1):176. Epub 2020 Jul 9.

GEOMAR Helmholtz Centre for Ocean Research Kiel, Kiel, Germany.

Bathymetry (seafloor depth), is a critical parameter providing the geospatial context for a multitude of marine scientific studies. Since 1997, the International Bathymetric Chart of the Arctic Ocean (IBCAO) has been the authoritative source of bathymetry for the Arctic Ocean. IBCAO has merged its efforts with the Nippon Foundation-GEBCO-Seabed 2030 Project, with the goal of mapping all of the oceans by 2030. Here we present the latest version (IBCAO Ver. 4.0), with more than twice the resolution (200 × 200 m versus 500 × 500 m) and with individual depth soundings constraining three times more area of the Arctic Ocean (∼19.8% versus 6.7%), than the previous IBCAO Ver. 3.0 released in 2012. Modern multibeam bathymetry comprises ∼14.3% in Ver. 4.0 compared to ∼5.4% in Ver. 3.0. Thus, the new IBCAO Ver. 4.0 has substantially more seafloor morphological information that offers new insights into a range of submarine features and processes; for example, the improved portrayal of Greenland fjords better serves predictive modelling of the fate of the Greenland Ice Sheet.
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http://dx.doi.org/10.1038/s41597-020-0520-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347603PMC
July 2020

Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate.

Nat Commun 2020 07 8;11(1):3412. Epub 2020 Jul 8.

Centre for Inflammation Biology and Cancer Immunology, School of Immunology and Microbial Sciences, King's College London, London, SE1 1UL, UK.

Regulatory B cells restrict immune and inflammatory responses across a number of contexts. This capacity is mediated primarily through the production of IL-10. Here we demonstrate that the induction of a regulatory program in human B cells is dependent on a metabolic priming event driven by cholesterol metabolism. Synthesis of the metabolic intermediate geranylgeranyl pyrophosphate (GGPP) is required to specifically drive IL-10 production, and to attenuate Th1 responses. Furthermore, GGPP-dependent protein modifications control signaling through PI3Kδ-AKT-GSK3, which in turn promote BLIMP1-dependent IL-10 production. Inherited gene mutations in cholesterol metabolism result in a severe autoinflammatory syndrome termed mevalonate kinase deficiency (MKD). Consistent with our findings, B cells from MKD patients induce poor IL-10 responses and are functionally impaired. Moreover, metabolic supplementation with GGPP is able to reverse this defect. Collectively, our data define cholesterol metabolism as an integral metabolic pathway for the optimal functioning of human IL-10 producing regulatory B cells.
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http://dx.doi.org/10.1038/s41467-020-17179-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343868PMC
July 2020
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