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  1. Book: Oxford handbook of endocrinology and diabetes

    Turner, Helen E.

    (Oxford handbooks ; Oxford medical publications)

    2009  

    Title variant Endocrinology and diabetes
    Author's details ed. by Helen Turner
    Series title Oxford handbooks
    Oxford medical publications
    Keywords Endocrine System Diseases ; Diabetes Mellitus ; Endocrinology ; Diabetes
    Subject code 616.4
    Language English
    Size XLIII, 902 S. : Ill., graph. Darst., 18cm
    Edition 2. ed.
    Publisher Oxford Univ. Press
    Publishing place Oxford u.a.
    Publishing country Great Britain
    Document type Book
    Note Previous ed.: 2002
    HBZ-ID HT015900014
    ISBN 978-0-19-856739-4 ; 0-19-856739-1
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: Analysis of a streamlined pathway for aortic surveillance for Turner syndrome in a single centre.

    Glatzel, Hannah / Njue, Faith / Turner, Helen E / Orchard, Elizabeth

    Clinical endocrinology

    2023  Volume 99, Issue 6, Page(s) 579–585

    Abstract: ... with Turner syndrome (TS) but predicting those with this heightened risk is difficult. In response to this, we sought ...

    Abstract Background and objective: The risk of aortic dissection (AoD) is increased in women with Turner syndrome (TS) but predicting those with this heightened risk is difficult. In response to this, we sought to create a pathway to monitor TS patients to improve efficiency and resource utilisation in our dedicated TS clinic, and to monitor more closely those women thought to be at increased risk of AoD.
    Design and patients: Our pathway was designed based on evidence derived from International Guidelines for the management of aortic disease in women with TS. Women were divided according to those with known risk factors for AoD, and those with no known risk factors. These groups were further subdivided into 4 pathways depending on ascending aortic size which in-turn determined the frequency of outpatient appointments and imaging.
    Results: Out of the 168 patients included in the analysis, 7 have had ascending aorta replacements, all in the highest risk group. Of the remaining 4 patients in the highest risk groups: 1 dissected whilst awaiting planned aortic surgery, 1 is currently awaiting surgery, 1 has low body mass index, therefore, making her aorta proportionally larger but not necessitating surgery and one has declined surgery. No women changed pathways.
    Conclusion: The risk-stratified pathway safely allowed consolidation of resources to women perceived to be at highest risk of AoD (excluding pregnancy), supporting the efficacy of the pathway and allowing the diversion of resources to those most at risk of AoD.
    MeSH term(s) Pregnancy ; Humans ; Female ; Turner Syndrome/complications ; Aorta, Thoracic ; Aorta ; Aortic Dissection ; Aortic Diseases/etiology
    Language English
    Publishing date 2023-09-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 121745-8
    ISSN 1365-2265 ; 0300-0664
    ISSN (online) 1365-2265
    ISSN 0300-0664
    DOI 10.1111/cen.14968
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Orthodontic treatment for prominent lower front teeth (Class III malocclusion) in children.

    Owens, Darren / Watkinson, Simon / Harrison, Jayne E / Turner, Sarah / Worthington, Helen V

    The Cochrane database of systematic reviews

    2024  Volume 4, Page(s) CD003451

    Abstract: ... involve a surgical component; these go through the gum into the bone (e.g. miniplates). In severe cases ... outcome was overjet (i.e. prominence of the lower front teeth); our secondary outcomes included ANB ...

    Abstract Background: Prominent lower front teeth (Class III malocclusion) may be due to jaw or tooth position or both. The upper jaw (maxilla) can be too far back or the lower jaw (mandible) too far forward; the upper front teeth (incisors) may be tipped back or the lower front teeth tipped forwards. Orthodontic treatment uses different types of braces (appliances) fitted inside or outside the mouth (or both) and fixed to the teeth. A facemask is the most commonly reported non-surgical intervention used to correct Class III malocclusion. The facemask rests on the forehead and chin, and is connected to the upper teeth via an expansion appliance (known as 'rapid maxillary expansion' (RME)). Using elastic bands placed by the wearer, a force is applied to the top teeth and jaw to pull them forwards and downward. Some orthodontic interventions involve a surgical component; these go through the gum into the bone (e.g. miniplates). In severe cases, or if orthodontic treatment is unsuccessful, people may need jaw (orthognathic) surgery as adults. This review updates one published in 2013.
    Objectives: To assess the effects of orthodontic treatment for prominent lower front teeth in children and adolescents.
    Search methods: An information specialist searched four bibliographic databases and two trial registries up to 16 January 2023. Review authors screened reference lists.
    Selection criteria: We looked for randomised controlled trials (RCTs) involving children and adolescents (16 years of age or under) randomised to receive orthodontic treatment to correct prominent lower front teeth (Class III malocclusion), or no (or delayed) treatment.
    Data collection and analysis: We used standard methodological procedures expected by Cochrane. Our primary outcome was overjet (i.e. prominence of the lower front teeth); our secondary outcomes included ANB (A point, nasion, B point) angle (which measures the relative position of the maxilla to the mandible).
    Main results: We identified 29 RCTs that randomised 1169 children (1102 analysed). The children were five to 13 years old at the start of treatment. Most studies measured outcomes directly after treatment; only one study provided long-term follow-up. All studies were at high risk of bias as participant and personnel blinding was not possible. Non-surgical orthodontic treatment versus untreated control We found moderate-certainty evidence that non-surgical orthodontic treatments provided a substantial improvement in overjet (mean difference (MD) 5.03 mm, 95% confidence interval (CI) 3.81 to 6.25; 4 studies, 184 participants) and ANB (MD 3.05°, 95% CI 2.40 to 3.71; 8 studies, 345 participants), compared to an untreated control group, when measured immediately after treatment. There was high heterogeneity in the analyses, but the effects were consistently in favour of the orthodontic treatment groups rather than the untreated control groups (studies tested facemask (with or without RME), chin cup, orthodontic removable traction appliance, tandem traction bow appliance, reverse Twin Block with lip pads and RME, Reverse Forsus and mandibular headgear). Longer-term outcomes were measured in only one study, which evaluated facemask. It presented low-certainty evidence that improvements in overjet and ANB were smaller at 3-year follow-up than just after treatment (overjet MD 2.5 mm, 95% CI 1.21 to 3.79; ANB MD 1.4°, 95% CI 0.43 to 2.37; 63 participants), and were not found at 6-year follow-up (overjet MD 1.30 mm, 95% CI -0.16 to 2.76; ANB MD 0.7°, 95% CI -0.74 to 2.14; 65 participants). In the same study, at the 6-year follow-up, clinicians made an assessment of whether surgical correction of participants' jaw position was likely to be needed in the future. A perceived need for surgical correction was observed more often in participants who had not received facemask treatment (odds ratio (OR) 3.34, 95% CI 1.21 to 9.24; 65 participants; low-certainty evidence). Surgical orthodontic treatment versus untreated control One study of 30 participants evaluated surgical miniplates, with facemask or Class III elastics, against no treatment, and found a substantial improvement in overjet (MD 7.96 mm, 95% CI 6.99 to 8.40) and ANB (MD 5.20°, 95% CI 4.48 to 5.92; 30 participants). However, the evidence was of low certainty, and there was no follow-up beyond the end of treatment. Facemask versus another non-surgical orthodontic treatment Eight studies compared facemask or modified facemask (with or without RME) to another non-surgical orthodontic treatment. Meta-analysis did not suggest that other treatments were superior; however, there was high heterogeneity, with mixed, uncertain findings (very low-certainty evidence). Facemask versus surgically-anchored appliance There may be no advantage of adding surgical anchorage to facemasks for ANB (MD -0.35, 95% CI -0.78 to 0.07; 4 studies, 143 participants; low-certainty evidence). The evidence for overjet was of very low certainty (MD -0.40 mm, 95% CI -1.30 to 0.50; 1 study, 43 participants). Facemask variations Adding RME to facemask treatment may have no additional benefit for ANB (MD -0.15°, 95% CI -0.94 to 0.64; 2 studies, 60 participants; low-certainty evidence). The evidence for overjet was of low certainty (MD 1.86 mm, 95% CI 0.39 to 3.33; 1 study, 31 participants). There may be no benefit in terms of effect on ANB of alternating rapid maxillary expansion and constriction compared to using expansion alone (MD -0.46°, 95% CI -1.03 to 0.10; 4 studies, 131 participants; low-certainty evidence).
    Authors' conclusions: Moderate-certainty evidence showed that non-surgical orthodontic treatments (which included facemask, reverse Twin Block, orthodontic removable traction appliance, chin cup, tandem traction bow appliance and mandibular headgear) improved the bite and jaw relationship immediately post-treatment. Low-certainty evidence showed surgical orthodontic treatments were also effective. One study measured longer-term outcomes and found that the benefit from facemask was reduced three years after treatment, and appeared to be lost by six years. However, participants receiving facemask treatment were judged by clinicians to be less likely to need jaw surgery in adulthood. We have low confidence in these findings and more studies are required to reach reliable conclusions. Orthodontic treatment for Class III malocclusion can be invasive, expensive and time-consuming, so future trials should include measurement of adverse effects and patient satisfaction, and should last long enough to evaluate whether orthodontic treatment in childhood avoids the need for jaw surgery in adulthood.
    MeSH term(s) Adolescent ; Child ; Humans ; Child, Preschool ; Orthodontics, Corrective ; Orthodontic Appliances ; Malocclusion, Angle Class III/therapy ; Dental Care ; Mouth
    Language English
    Publishing date 2024-04-10
    Publishing country England
    Document type Meta-Analysis ; Systematic Review ; Journal Article ; Review
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD003451.pub3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Risk assessment for aortic dissection in Turner syndrome: The role of the aortic growth rate.

    Calanchini, Matilde / Bradley-Watson, James / McMillan, Fiona / Myerson, Saul / Fabbri, Andrea / Turner, Helen E / Orchard, Elizabeth

    Clinical endocrinology

    2024  Volume 100, Issue 3, Page(s) 269–276

    Abstract: Objective: The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting ...

    Abstract Objective: The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year. To investigate the aortic growth rate in TS and TS-related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement.
    Methods: 151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts.
    Results: 70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS-related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac-alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post-operatively.
    Conclusions: Mean aortic growth in our TS population was increased compared to non-TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD.
    MeSH term(s) Adult ; Female ; Humans ; Adolescent ; Young Adult ; Turner Syndrome/complications ; Turner Syndrome/epidemiology ; Retrospective Studies ; Aortic Dissection ; Aortic Diseases/complications ; Aortic Diseases/epidemiology ; Risk Assessment
    Language English
    Publishing date 2024-01-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 121745-8
    ISSN 1365-2265 ; 0300-0664
    ISSN (online) 1365-2265
    ISSN 0300-0664
    DOI 10.1111/cen.15017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit all?

    Advani, Sonali D / North, Rebecca / Turner, Nicholas A / Ahmadi, Sahra / Denniss, Julia / Francis, Adero / Johnson, Rachel / Hasan, Anum / Mirza, Faryal / Pardue, Sarah / Rao, Meghana / Rosshandler, Yasmin / Tang, Helen / Schmader, Kenneth E / Anderson, Deverick J

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2024  

    Abstract: In a multi-hospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ... ...

    Abstract In a multi-hospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.
    Language English
    Publishing date 2024-04-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciae230
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Historical plant introductions predict current insect invasions.

    Bonnamour, Aymeric / Blake, Rachael E / Liebhold, Andrew M / Nahrung, Helen F / Roques, Alain / Turner, Rebecca M / Yamanaka, Takehiko / Bertelsmeier, Cleo

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 24, Page(s) e2221826120

    Abstract: Thousands of insect species have been introduced outside of their native ranges, and some of them strongly impact ecosystems and human societies. Because a large fraction of insects feed on or are associated with plants, nonnative plants provide habitat ... ...

    Abstract Thousands of insect species have been introduced outside of their native ranges, and some of them strongly impact ecosystems and human societies. Because a large fraction of insects feed on or are associated with plants, nonnative plants provide habitat and resources for invading insects, thereby facilitating their establishment. Furthermore, plant imports represent one of the main pathways for accidental nonnative insect introductions. Here, we tested the hypothesis that plant invasions precede and promote insect invasions. We found that geographical variation in current nonnative insect flows was best explained by nonnative plant flows dating back to 1900 rather than by more recent plant flows. Interestingly, nonnative plant flows were a better predictor of insect invasions than potentially confounding socioeconomic variables. Based on the observed time lag between plant and insect invasions, we estimated that the global insect invasion debt consists of 3,442 region-level introductions, representing a potential increase of 35% of insect invasions. This debt was most important in the Afrotropics, the Neotropics, and Indomalaya, where we expect a 10 to 20-fold increase in discoveries of new nonnative insect species. Overall, our results highlight the strong link between plant and insect invasions and show that limiting the spread of nonnative plants might be key to preventing future invasions of both plants and insects.
    MeSH term(s) Animals ; Plants ; Insecta ; Introduced Species
    Language English
    Publishing date 2023-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2221826120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Tumour occurrence in women with Turner syndrome: A narrative review and single-centre case series.

    Mathara Diddhenipothage, Shani A D / Goindoo, Ryan J / Bragg, Fiona / Orchard, Elizabeth / Shears, Deborah / Calanchini, Matilde / Turner, Helen E

    Clinical endocrinology

    2023  Volume 99, Issue 1, Page(s) 64–72

    Abstract: Background: Population studies suggest cancer morbidity may be different in Turner syndrome (TS ...

    Abstract Background: Population studies suggest cancer morbidity may be different in Turner syndrome (TS) compared to the background female population. However, significant variability is observed in cancer associations likely due to heterogeneity in patient cohorts. We explored the prevalence and patterns of cancer amongst a cohort of women with TS attending a dedicated TS clinic.
    Methods: Retrospective analysis of the patient database was performed to identify TS women who developed cancer. Population data (available before 2015) from the National Cancer Registration and Analysis Service database were used for comparison.
    Results: Out of 156 TS women, median age of 32 (range 18-73) years, 9 (5.8%) had a recorded cancer diagnosis. Types of cancers were, bilateral gonadoblastoma, type 1 gastric neuroendocrine tumour (NET), appendiceal-NET, gastrointestinal stromal tumour, plasma cell dyscrasia, synovial sarcoma, cervical cancer, medulloblastoma and aplastic anaemia. Median age at cancer diagnosis was 35 (range 7-58) years and two were detected incidentally. Five women had 45,X karyotype, three received growth hormone treatment and all except one received oestrogen replacement therapy. The cancer prevalence of the background age-matched female population was 4.4%.
    Conclusions: We confirm the previous observations that women with TS do not appear to be at overall increased risk of common malignancies. Our small cohort showed a spectrum of rare malignancies that are not typically associated with TS, except for a single patient with a gonadoblastoma. The slightly higher prevalence of cancer in our cohort might simply represent increased cancer prevalence in the background population, or might be related to small sample size and regular monitoring of these women due to TS per se.
    MeSH term(s) Humans ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Ovarian Neoplasms ; Turner Syndrome ; Retrospective Studies
    Language English
    Publishing date 2023-03-20
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 121745-8
    ISSN 1365-2265 ; 0300-0664
    ISSN (online) 1365-2265
    ISSN 0300-0664
    DOI 10.1111/cen.14910
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Use of Airborne Laser Scanning to assess effects of understorey vegetation structure on nest‐site selection and breeding performance in an Australian passerine bird

    Richard S. Turner / Ophélie J. D. Lasne / Kara N. Youngentob / Shukhrat Shokirov / Helen L. Osmond / Loeske E. B. Kruuk

    Remote Sensing in Ecology and Conservation, Vol 9, Iss 6, Pp 787-

    2023  Volume 802

    Abstract: Abstract In wild bird populations, the structure of vegetation around nest‐sites can influence the risk of predation of dependent offspring, generating selection for nest‐sites with vegetation characteristics associated with lower predation rates. ... ...

    Abstract Abstract In wild bird populations, the structure of vegetation around nest‐sites can influence the risk of predation of dependent offspring, generating selection for nest‐sites with vegetation characteristics associated with lower predation rates. However, vegetation structure can be difficult to quantify objectively in the field, which might explain why there remains a general lack of understanding of which characteristics are most important in determining predation rates. Airborne laser scanning (ALS) offers a powerful means of measuring vegetation structure at unprecedented resolution. Here, we combined ALS with 11 years of breeding data from a wild population of superb fairy‐wrens Malurus cyaneus in southeastern Australia, a species which nests relatively close to the ground and has high rates of nest and fledgling predation. We derived structural measurements of understorey (0–8 m) vegetation from a contiguous grid of 30 × 30 m resolution cells across our c. 65 hectares study area. We found that cells with nests (nest‐cells) differed in their understorey vegetation structure characteristics compared to unused cells, primarily in having denser vegetation in the lowest layer of the understorey (0–2 m; the ‘groundstorey’ layer). The average height of understorey vegetation was also lower in cells with nests than in those without nests. However, relationships between understorey vegetation structure characteristics and breeding performance were mixed. Nest success rates decreased with higher volumes of groundstorey vegetation, as did fledgling survival rates, though only in nest‐cells with lower height vegetation. Our results indicate that ALS can identify vegetation characteristics relevant for superb fairy‐wren nest‐site selection, but that nesting preferences are not beneficial under current predation pressures. The study illustrates the potential for using ALS to investigate how ecological conditions affect behaviour and life‐histories in wild animal populations.
    Keywords Airborne laser scanning ; avian breeding performance ; LiDAR ; nest predation ; nest‐site selection ; vegetation structure ; Technology ; T ; Ecology ; QH540-549.5
    Subject code 590
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Ambulatory microdose induction of buprenorphine-naloxone in two adolescent patients with sickle cell disease.

    Buchheit, Bradley M / Joslin, Timothy / Turner, Helen N / Wong, Trisha E

    Pediatric blood & cancer

    2020  Volume 68, Issue 1, Page(s) e28766

    Abstract: Sickle cell disease (SCD) is a hematologic disorder defined by presence of sickle-shaped red blood cells that can occlude blood vessels and cause tissue ischemia and pain. Treating SCD pain adequately and safely is difficult given today's opioid climate. ...

    Abstract Sickle cell disease (SCD) is a hematologic disorder defined by presence of sickle-shaped red blood cells that can occlude blood vessels and cause tissue ischemia and pain. Treating SCD pain adequately and safely is difficult given today's opioid climate. Buprenorphine-naloxone has been described as an alternative option to treat chronic pain in the adult literature; however, it historically required discontinuation of full-agonist opioids before initiation, resulting in opioid withdrawal. Herein we present two adolescents with SCD who successfully weaned off large doses of full-agonist opioids by using microdose induction of buprenorphine-naloxone in clinic, without experiencing significant opioid withdrawal. Ambulatory microdose induction may remove hurdles that otherwise would discourage patients from trying this regimen while still controlling pain safely.
    MeSH term(s) Adolescent ; Adult ; Analgesics, Opioid/therapeutic use ; Anemia, Sickle Cell/complications ; Buprenorphine, Naloxone Drug Combination/therapeutic use ; Dose-Response Relationship, Drug ; Humans ; Male ; Pain/drug therapy ; Pain/etiology ; Pain/pathology ; Prognosis ; Young Adult
    Chemical Substances Analgesics, Opioid ; Buprenorphine, Naloxone Drug Combination
    Language English
    Publishing date 2020-10-27
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.28766
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Microglial CD68 and L-ferritin upregulation in response to phosphorylated-TDP-43 pathology in the amyotrophic lateral sclerosis brain.

    Swanson, Molly E V / Mrkela, Miran / Murray, Helen C / Cao, Maize C / Turner, Clinton / Curtis, Maurice A / Faull, Richard L M / Walker, Adam K / Scotter, Emma L

    Acta neuropathologica communications

    2023  Volume 11, Issue 1, Page(s) 69

    Abstract: Microglia, the innate immune cells of the brain, are activated by damage or disease. In mouse models of amyotrophic lateral sclerosis (ALS), microglia shift from neurotrophic to neurotoxic states with disease progression. It remains unclear how human ... ...

    Abstract Microglia, the innate immune cells of the brain, are activated by damage or disease. In mouse models of amyotrophic lateral sclerosis (ALS), microglia shift from neurotrophic to neurotoxic states with disease progression. It remains unclear how human microglia change relative to the TAR DNA-binding protein 43 (TDP-43) aggregation that occurs in 97% of ALS cases. Here we examine spatial relationships between microglial activation and TDP-43 pathology in brain tissue from people with ALS and from a TDP-43-driven ALS mouse model. Post-mortem human brain tissue from the Neurological Foundation Human Brain Bank was obtained from 10 control and 10 ALS cases in parallel with brain tissue from a bigenic NEFH-tTA/tetO-hTDP-43∆NLS (rNLS) mouse model of ALS at disease onset, early disease, and late disease stages. The spatiotemporal relationship between microglial activation and ALS pathology was determined by investigating microglial functional marker expression in brain regions with low and high TDP-43 burden at end-stage human disease: hippocampus and motor cortex, respectively. Sections were immunohistochemically labelled with a two-round multiplexed antibody panel against; microglial functional markers (L-ferritin, HLA-DR, CD74, CD68, and Iba1), a neuronal marker, an astrocyte marker, and pathological phosphorylated TDP-43 (pTDP-43). Single-cell levels of microglial functional markers were quantified using custom analysis pipelines and mapped to anatomical regions and ALS pathology. We identified a significant increase in microglial Iba1 and CD68 expression in the human ALS motor cortex, with microglial CD68 being significantly correlated with pTDP-43 pathology load. We also identified two subpopulations of microglia enriched in the ALS motor cortex that were defined by high L-ferritin expression. A similar pattern of microglial changes was observed in the rNLS mouse, with an increase first in CD68 and then in L-ferritin expression, with both occurring only after pTDP-43 inclusions were detectable. Our data strongly suggest that microglia are phagocytic at early-stage ALS but transition to a dysfunctional state at end-stage disease, and that these functional states are driven by pTDP-43 aggregation. Overall, these findings enhance our understanding of microglial phenotypes and function in ALS.
    MeSH term(s) Humans ; Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology ; Microglia/metabolism ; Apoferritins/metabolism ; Up-Regulation ; Brain/pathology ; DNA-Binding Proteins/metabolism
    Chemical Substances Apoferritins (9013-31-4) ; DNA-Binding Proteins ; TDP-43 protein, mouse
    Language English
    Publishing date 2023-04-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2715589-4
    ISSN 2051-5960 ; 2051-5960
    ISSN (online) 2051-5960
    ISSN 2051-5960
    DOI 10.1186/s40478-023-01561-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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