Medin co-aggregates with vascular amyloid-ß in Alzheimer's disease.

Aggregates of medin amyloid (a fragment of the protein MFG-E8, also known as lactadherin) are found in the vasculature of almost all humans over 50 years of age1,2, making it the most common amyloid currently known. We recently reported that medin also aggregates in blood vessels of ageing wild-type mice, causing cerebrovascular dysfunction3. Here we demonstrate in amyloid-ß precursor protein (APP) transgenic mice and in patients with Alzheimer's disease that medin co-localizes with vascular amyloid-ß deposits, and that in mice, medin deficiency reduces vascular amyloid-ß deposition by half. Moreover, in both the mouse and human brain, MFG-E8 is highly enriched in the vasculature and both MFG-E8 and medin levels increase with the severity of vascular amyloid-ß burden. Additionally, analysing data from 566 individuals in the ROSMAP cohort, we find that patients with Alzheimer's disease have higher MFGE8 expression levels, which are attributable to vascular cells and are associated with increased measures of cognitive decline, independent of plaque and tau pathology. Mechanistically, we demonstrate that medin interacts directly with amyloid-ß to promote its aggregation, as medin forms heterologous fibrils with amyloid-ß, affects amyloid-ß fibril structure, and cross-seeds amyloid-ß aggregation both in vitro and in vivo. Thus, medin could be a therapeutic target for prevention of vascular damage and cognitive decline resulting from amyloid-ß deposition in the blood vessels of the brain.

Incidental finding of a human-like tusavirus in a lamb with lip lesions and fatal pneumonia.

Tusaviruses in the genus Protoparvovirus of family Parvoviridae were first identified in a diarrhoeic Tunisian child in 2014. Thereafter, high prevalence of a genetically similar virus was demonstrated in faeces from caprine and ovine species in Hungary. Here, we describe an investigation into the cause of scabby lip lesions in a 6 month-old lamb, submitted from a farm experiencing weight loss and scouring in lambs in England. Transmission electron microscopy visualised small circular particles of 18 and 22 nm in diameter in lip lesions identified as tusavirus and flumine parvovirus by Next Generation Sequencing. Liver, kidney, lung, small intestine content and faeces were also strongly positive for the tusavirus DNA as well as 10 % of faecal samples of the flock collected 2 months after the initial lip sampling. NS1 and VP1 amino acid sequences of this tusavirus displayed 99.5 and 92.89 % identity to those of a human tusavirus, respectively. These amino acid identities were at 95.5 and 89.68 % when compared to those of a goat tusavirus. Phylogenetic analysis of the NS1 and VP1 also grouped the virus in the genus Protoparvovirus and close to tusaviruses detected in human, ovine and caprine species. Wider surveillance of the virus indicated a broader geographical distribution for the virus in England. Histology of the lip tissue revealed localised areas of epidermal hyperplasia and hyperkeratosis affecting haired skin, with mild leucocyte infiltration of the subjacent dermis, but no changes to implicate virus involvement. Flumine parvovirus was concluded to be an environment contaminant. Broader studies in prevalence of these virus in UK sheep flocks and human population, animal models and experimental infections could provide insights into the pathogenesis of these novel viruses and their zoonotic potential.

Children and adolescents with type 1 diabetes in Aotearoa New Zealand: An online survey of workforce and outcomes 2021.

AIMS: To survey the national workforce that manages children and adolescents with type 1 diabetes (T1D) in Aotearoa New Zealand and compare with glycaemic outcomes for 2021. METHODS: A representative from each tertiary and regional diabetes service in Aotearoa New Zealand was asked to participate in an online survey assessing health-care professional (HCP) workforce numbers operating for the 2021 calendar year. Regional full-time-equivalent (FTE), glycaemic outcomes and population demographics were compared to a previously reported workforce surveys (2015 and 2019). RESULTS: Seventeen sites responded - including all four large tertiary centres - serving >99% of children and adolescents with T1D in Aotearoa New Zealand. HCP resourcing varied across sites, with median (range) HCP/100 patient ratios of: doctors: 0.40 (0.16-1.11), nurses: 1.19 (0.29-5.56), dietitians: 0.25 (0-1.11) and psychologist/social workers: 0 (0-0.26). No site met all of the International Society of Paediatric and Adolescent Diabetes (ISPAD) recommendations of HCP/100 patient ratios. Measures of socio-economic deprivation predicted HbA1c, rather than the diabetes clinic attended. Overall, only 15.1% (240/1585) of patients had an HbA1c less than the recommended 53 mmol/mol. CONCLUSIONS: The Aotearoa New Zealand workforce for children and adolescents with T1D is under-resourced and no site meets the ISPAD recommendations. There has been no significant increase in HCP/100 patient ratios compared to previous workforce surveys over the last decade. Few children and adolescents with T1D meet the recommended HbA1c. Resourcing according to recommended clinical need is required if equity in outcomes for young people with T1D is to be addressed.

Prevalence and incidence of type 1 diabetes in children aged 0-14 years old in New Zealand in 2021.

AIM: National prevalence and incidence data are important for understanding population trends and allocating health-care resources. We aimed to provide a current national snapshot of prevalence and annual incidence rates for children aged 0-14 with type 1 diabetes (T1D) in Aotearoa New Zealand and to identify differences associated with demographic variables. METHODS: Paediatric diabetes centres across Aotearoa were invited to record anonymised demographic and diabetes data on children under their services between 1 October 2020 and 30 September 2021. National prevalence and incidence were calculated using usually resident population counts from the 2018 census. The effect of ethnicity on prevalence and incidence was assessed using Poisson regression. RESULTS: There were 1209 children aged 0-14 with T1D in October 2021. The national prevalence was 131/100 000 (95% confidence interval (CI) 124-139). European children had twice the prevalence as those of Maori or Pacific ethnicity (P < 0.001). There was no effect by gender (P = 0.3) and prevalence predictably increased with age. The annualised incidence of T1D was 23/100 000 (95% CI 20-26). European children were 2.6 times as likely as Maori children to be diagnosed with T1D in that year (incidence rate ratio = 2.6, 95% CI 1.7-4.2). Regional differences in prevalence and incidence were noted, potentially due to the ethnicity differences across regions. Unadjusted prevalence and incidence decreased with lower socio-economic status, likely due to an over-representation of non-Europeans living in the most deprived areas. CONCLUSIONS: T1D affects an ethnically diverse population in Aotearoa and important regional differences exist that may impact workforce planning.

Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice.

Medin is the most common amyloid known in humans, as it can be found in blood vessels of the upper body in virtually everybody over 50 years of age. However, it remains unknown whether deposition of Medin plays a causal role in age-related vascular dysfunction. We now report that aggregates of Medin also develop in the aorta and brain vasculature of wild-type mice in an age-dependent manner. Strikingly, genetic deficiency of the Medin precursor protein, MFG-E8, eliminates not only vascular aggregates but also prevents age-associated decline of cerebrovascular function in mice. Given the prevalence of Medin aggregates in the general population and its role in vascular dysfunction with aging, targeting Medin may become a novel approach to sustain healthy aging.

Clinical Risk Factors Associated With Late-Onset Invasive Group B Streptococcal Disease: Systematic Review and Meta-Analyses.

BACKGROUND: Group B streptococcal (GBS) infection remains one of the most significant causes of late-onset sepsis and meningitis (LOGBS) among young infants. However, transmission routes and risk factors for LOGBS are not yet fully understood. METHODS: We conducted systematic reviews on clinical risk factors previously reported in the literature (prematurity, low birth weight [<2500 g], antenatal colonization, multiple-gestation pregnancy, maternal age <20 years, male infant sex, intrapartum fever, prolonged rupture of membranes) and meta-analyses to determine pooled estimates of risk. RESULTS: We included 27 articles, reporting 5315 cases. Prematurity (odds ratio [OR] 5.66; 95% confidence interval [CI]: 4.43-7.22), low birth weight (OR 6.73; 95% CI: 4.68-9.67), maternal colonization (2.67; [2.07-3.45]), and multiple-gestation pregnancies (OR 8.01; 95% CI: 5.19-12.38) were associated with an increased risk of LOGBS. CONCLUSIONS: Prematurity/low birth weight and maternal colonization are major risk factors for LOGBS. Future GBS vaccine studies should try to establish the optimal time for vaccination during pregnancy to protect preterm infants.

COVID-19 deaths in children and young people in England, March 2020 to December 2021: An active prospective national surveillance study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. METHODS AND FINDINGS: CYP aged <20 years who died within 100 days of laboratory-confirmed SARS-CoV-2 infection between 01 March 2020 and 31 December 2021 in England were followed up in detail, using national databases, surveillance questionnaires, post-mortem reports, and clinician interviews. There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged <20 years, with an infection fatality rate of 0.70/100,000 SARS-CoV-2 infections in this age group estimated through real-time, nowcasting modelling, and a mortality rate of 0.61/100,000. Limitations include possible under-ascertainment of deaths in CYP who were not tested for SARS-CoV-2 and lack of direct access to clinical data for hospitalised CYP. CONCLUSIONS: COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.

Is There Enough Evidence to Support the Role of Glycosaminoglycans and Proteoglycans in Thoracic Aortic Aneurysm and Dissection?-A Systematic Review.

Altered proteoglycan (PG) and glycosaminoglycan (GAG) distribution within the aortic wall has been implicated in thoracic aortic aneurysm and dissection (TAAD). This review was conducted to identify literature reporting the presence, distribution and role of PGs and GAGs in the normal aorta and differences associated with sporadic TAAD to address the question; is there enough evidence to establish the role of GAGs/PGs in TAAD? 75 studies were included, divided into normal aorta (n = 51) and TAAD (n = 24). There is contradictory data regarding changes in GAGs upon ageing; most studies reported an increase in GAG sub-types, often followed by a decrease upon further ageing. Fourteen studies reported changes in PG/GAG or associated degradation enzyme levels in TAAD, with most increased in disease tissue or serum. We conclude that despite being present at relatively low abundance in the aortic wall, PGs and GAGs play an important role in extracellular matrix maintenance, with differences observed upon ageing and in association with TAAD. However, there is currently insufficient information to establish a cause-effect relationship with an underlying mechanistic understanding of these changes requiring further investigation. Increased PG presence in serum associated with aortic disease highlights the future potential of these biomolecules as diagnostic or prognostic biomarkers.

A novel dicistrovirus in a captive red squirrel (Sciurus vulgaris).

Dicistroviruses are single-stranded RNA viruses in the family Dicistroviridae. The viruses have mainly been detected in arthropods and are the cause of several devastating diseases in many of these species such as honeybees. Increasingly, dicistroviruses have also been detected in both mammalian and avian species in faeces, blood and liver, but with unconfirmed pathology. Here, we report a novel dicistrovirus detected in the intestinal content of a captive red squirrel with enteritis along with the disease history, pathology and genomic characterisation of the virus. Virus particle morphology resembled those of picornaviruses with a diameter of 28-32 nm but failed to be detected using a mammalian/avian pan viral microarray. Next-generation sequencing confirmed a dicistrovirus having a typical dicistrovirus genome organization, but with the polyprotein 1 being shorter by about 100 amino acids, compared to that of other dicistroviruses. Phylogenetic analysis of ORF1 and ORF2 sequences clustered the virus with two yet unassigned dicistroviruses detected in Gorilla gorilla and a freshwater arthropod and likely to be designated to a new genus. Our data further highlights the ever-growing diversity of dicistroviruses, but the clinical significance of the virus in mammalian species and particularly red squirrels has yet to be established.

Medin Oligomer Membrane Pore Formation: A Potential Mechanism of Vascular Dysfunction.

Medin, a 50-amino-acid cleavage product of the milk fat globule-EGF factor 8 protein, is one of the most common forms of localized amyloid found in the vasculature of individuals older than 50 years. Medin induces endothelial dysfunction and vascular inflammation, yet despite its prevalence in the human aorta and multiple arterial beds, little is known about the nature of its pathology. Medin oligomers have been implicated in the pathology of aortic aneurysm, aortic dissection, and more recently, vascular dementia. Recent in vitro biomechanical measurements found increased oligomer levels in aneurysm patients with altered aortic wall integrity. Our results suggest an oligomer-mediated toxicity mechanism for medin pathology. Using lipid bilayer electrophysiology, we show that medin oligomers induce ionic membrane permeability by pore formation. Pore activity was primarily observed for preaggregated medin species from the growth-phase and rarely for lag-phase species. Atomic force microscopy (AFM) imaging of medin aggregates at different stages of aggregation revealed the gradual formation of flat domains resembling the morphology of supported lipid bilayers. Transmission electron microscopy images showed the coexistence of compact oligomers, largely consistent with the AFM data, and larger protofibrillar structures. Circular dichroism spectroscopy revealed the presence of largely disordered species and suggested the presence of ß-sheets. This observation and the significantly lower thioflavin T fluorescence emitted by medin aggregates compared to amyloid-ß fibrils, along with the absence of amyloid fibers in the AFM and transmission electron microscopy images, suggest that medin aggregation into pores follows a nonamyloidogenic pathway. In silico modeling by molecular dynamics simulations provides atomic-level structural detail of medin pores with the CNpNC barrel topology and diameters comparable to values estimated from experimental pore conductances.

Human cerebral collateral arteriole function in subjects with normal cognition, mild cognitive impairment, and dementia.

Clinical and preclinical studies have suggested a link between cardiovascular disease and dementia disorders, but the role of the collateral brain circulation in cognitive dysfunction remains unknown. We aimed to test the hypothesis that leptomeningeal arteriole (LMA) function and response to metabolic stressors differ among subjects with dementia, mild cognitive impairment (MCI), and normal cognition (CN). After rapid autopsy, LMAs were isolated from subjects with CN ( n = 10), MCI ( n = 12), or dementia [ n = 42, Alzheimer's disease (AD), vascular dementia (VaD), or other dementia], and endothelial and smooth muscle-dependent function were measured at baseline and after exposure to ß-amyloid (2 µM), palmitic acid (150 µM), or medin (5 µM) and compared. There were no differences among the groups in baseline endothelial function (maximum dilation to acetylcholine, CN: 74.1 ± 9.7%, MCI: 67.1 ± 4.8%, AD: 74.7 ± 2.8%, VaD: 72.0 ± 5.3%, and other dementia: 68.0 ± 8.0%) and smooth muscle-dependent function (CN: 93.4 ± 3.0%, MCI: 83.3 ± 4.1%, AD: 91.8 ± 1.7%, VaD: 91.7 ± 2.4%, and other dementia: 87.9 ± 4.9%). There was no correlation between last cognitive function score and baseline endothelial or smooth muscle-dependent function. LMA endothelial function and, to a lesser extent, smooth muscle-dependent function were impaired posttreatment with ß-amyloid, palmitic acid, and medin. Posttreatment LMA responses were not different between subjects with CN/MCI vs. dementia. Baseline responses and impaired vasoreactivity after treatment with metabolic stressors did not differ among subjects with CN, MCI, and dementia. The results suggest that the cognitive dysfunction in dementia disorders is not attributable to differences in baseline brain collateral circulation function but may be influenced by exposure of the vasculature to metabolic stressors.

Insights into the Origin of Distinct Medin Fibril Morphologies Induced by Incubation Conditions and Seeding.

Incubation conditions are an important factor to consider when studying protein aggregation in vitro. Here, we employed biophysical methods and atomic force microscopy to show that agitation dramatically alters the morphology of medin, an amyloid protein deposited in the aorta. Agitation reduces the lag time for fibrillation by ~18-fold, suggesting that the rate of fibril formation plays a key role in directing the protein packing arrangement within fibrils. Utilising preformed sonicated fibrils as seeds, we probed the role of seeding on medin fibrillation and revealed three distinct fibril morphologies, with biophysical modelling explaining the salient features of experimental observations. We showed that nucleation pathways to distinct fibril morphologies may be switched on and off depending on the properties of the seeding fibrils and growth conditions. These findings may impact on the development of amyloid-based biomaterials and enhance understanding of seeding as a pathological mechanism.

Comparisons with amyloid-ß reveal an aspartate residue that stabilizes fibrils of the aortic amyloid peptide medin.

Aortic medial amyloid (AMA) is the most common localized human amyloid, occurring in virtually all of the Caucasian population over the age of 50. The main protein component of AMA, medin, readily assembles into amyloid-like fibrils in vitro. Despite the prevalence of AMA, little is known about the self-assembly mechanism of medin or the molecular architecture of the fibrils. The amino acid sequence of medin is strikingly similar to the sequence of the Alzheimer disease (AD) amyloid-ß (Aß) polypeptides around the structural turn region of Aß, where mutations associated with familial, early onset AD, have been identified. Asp(25) and Lys(30) of medin align with residues Asp(23) and Lys(28) of Aß, which are known to form a stabilizing salt bridge in some fibril morphologies. Here we show that substituting Asp(25) of medin with asparagine (D25N) impedes assembly into fibrils and stabilizes non-cytotoxic oligomers. Wild-type medin, by contrast, aggregates into ß-sheet-rich amyloid-like fibrils within 50 h. A structural analysis of wild-type fibrils by solid-state NMR suggests a molecular repeat unit comprising at least two extended ß-strands, separated by a turn stabilized by a Asp(25)-Lys(30) salt bridge. We propose that Asp(25) drives the assembly of medin by stabilizing the fibrillar conformation of the peptide and is thus reminiscent of the influence of Asp(23) on the aggregation of Aß. Pharmacological comparisons of wild-type medin and D25N will help to ascertain the pathological significance of this poorly understood protein.

Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid.

The aggregation and fibril deposition of amyloid proteins have been implicated in a range of neurodegenerative and vascular diseases, and yet the underlying molecular mechanisms are poorly understood. Here, we use a combination of cell-based assays, biophysical analysis, and atomic force microscopy to investigate the potential involvement of oxidative stress in aortic medial amyloid (AMA) pathogenesis and deposition. We show that medin, the main constituent of AMA, can induce an environment rich in oxidative species, increasing superoxide and reducing bioavailable nitric oxide in human cells. We investigate the role that this oxidative environment may play in altering the aggregation process of medin and identify potential posttranslational modification sites where site-specific modification and interaction can be unambiguously demonstrated. In an oxidizing environment, medin is nitrated at tyrosine and tryptophan residues, with resultant effects on morphology that lead to longer fibrils with increased toxicity. This provides further motivation to investigate the role of oxidative stress in AMA pathogenicity.

Expression and purification of the aortic amyloid polypeptide medin.

The 50-amino acid protein medin is the main fibrillar component of human aortic medial amyloid (AMA), the most common form of localised amyloid which affects 97% of Caucasians over the age of 50. Structural models for several amyloid assemblies, including the Alzheimer's amyloid-ß peptides, have been defined from solid-state nuclear magnetic resonance (SSNMR) measurements on (13)C- and (15)N-labelled protein fibrils. SSNMR-derived structural information on fibrillar medin is scant, however, because studies to date have been restricted to limited measurements on site-specifically labelled protein prepared by solid-phase synthesis. Here we report a procedure for the expression of a SUMO-medin fusion protein in Escherichia coli and IMAC purification yielding pure, uniformly (13)C,(15)N-labelled medin in quantities required for SSNMR analysis. Thioflavin T fluorescence and dynamic light scattering measurements and transmission electron microscopy analysis confirm that recombinant medin assembles into amyloid-like fibrils over a 48-h period. The first (13)C and (15)N SSNMR spectra obtained for uniformly-labelled fibrils indicate that medin adopts a predominantly ß-sheet conformation with some unstructured elements, and provide the basis for further, more detailed structural investigations.

Heterosexual men's ratings of sexual attractiveness of pubescent girls: Effects of labeling the target as under or over the age of sexual consent.

The study aimed to identify implicit and explicit processes involved in reporting the sexual attractiveness of photographs of the same pubescent girls labeled as either under or within the age of sexual consent in the UK, women, and men. In two studies, 53 and 70 heterosexual men (M age 25.2 and 31.0 years) rated the sexual attractiveness of photographs in each category presented via computer [seeing target photographs of girls labeled as either under- (14-15 years) or within the age of consent (16-17 years)], using a 7-point response box. Ratings in Study 1 were in response to a question asking participants to rate how sexually attractive the person in each photograph was. In Study 2, participants rated how sexually attractive they personally found the target. Response times were also recorded. Several findings were replicated in both studies (although the strength of findings differed). Mean ratings of the sexual attractiveness of the underage girls were lower than those of overage girls and women. In addition, correlations revealed significantly longer responding times when "underage" girls (and men) were rated as more highly sexually attractive. No such relationship emerged with the same girls labeled within the age of consent or women. Overall, these data suggest that men find pubescent girls identified as being under the age of consent sexually attractive, but inhibit their willingness to report this; the greater the attraction, the greater the inhibition.

A local audit evaluating bone health in patients with functional hypothalamic amenorrhoea secondary to an eating disorder and a review of the application of hormone therapy in this clinical setting.

It is widely known that estrogen has a fundamental role to play in skeletal homeostasis. In the most reductionist sense, the action of estrogen can be surmised as anti-resorptive. Estrogen prevents the break-down of bone. It therefore follows that estrogen deficiency states, such as the menopause and functional hypothalamic amenorrhoea (FHA), are often characterised by increased bone remodelling and disrupted skeletal homeostasis. FHA is the cessation of menstruation secondary to abnormal signalling between the hypothalamus and pituitary gland due to deficient pulsatile secretion of Gonadotrophin Releasing Hormone (GnRH). Functional hypothalamic amenorrhoea is frequently a consequence of women suffering with eating disorders. The development of FHA secondary to eating disorders is an evolutionary adaptive response to chronic metabolic energy deficiency. Fundamentally, preservation of life is biologically prioritised over dispensable physiological process such as reproduction. Consequently, the hypothalamic-pituitary-ovarian (HPO) axis fails, which disrupts menstrual function and ovulation, culminating in a state of estrogen deficiency. One of the most important and long-lasting deleterious consequences of FHA is disrupted skeletal homeostasis and bone loss. Estrogen replacement, most commonly in the form of combined hormone replacement therapy (HRT) or the combined oral contraceptive pill (COCP), is advised for women with an early menopause to prevent bone loss. Arguably, estrogen replacement should also be utilised in the context of FHA. However, the optimum estrogen regime for women with FHA remains under-researched and so management is not evidence-based.

Emergent inequity of glycaemic metrics for Maori children with type 1 diabetes is negated by early use of continuous glucose monitoring.

AIM: We investigated if continuous glucose monitoring (CGM) in children with type 1 diabetes (T1D) within 12 months of being diagnosed modifies the development of glycaemic outcome inequity on the basis of either ethnicity or socio-economic status (SES). METHOD: De-identified clinical and SES data from the KIWIDIAB data network were collected 12 months after diagnosis in children under 15 years diagnosed with T1D between 1 October 2020 and 1 October 2021. RESULTS: There were 206 children with new onset T1D: CGM use was 56.7% for Maori and 77.2% for Europeans. Mean (SD) HbA1c was 62.4 (14.2) mmol/mol at 12 months post diagnosis, but Maori were 9.4mmol/mol higher compared to Europeans (p<0.001). For those without CGM, Maori had an HbA1c 10.8 (95% CI 2.3 to 19.4, p=0.013) mmol/mol higher than Europeans, whereas there was no evidence of a difference between Maori and Europeans using CGM (62.1 [9.3] mmol/mol vs 58.5 [12.4] mmol/mol p=0.53 respectively). Comparing quintiles of SES, HbA1c was 10.8 (95% CI 4.7 to 16.9, p<0.001) mmol/mol higher in the lowest quintile of SES compared to the highest. CONCLUSION: These observational data suggest CGM use ameliorates the ethnic disparity in HbA1c at 12 months in new onset T1D.

Prevalence and Molecular Analysis of Encephalomyocarditis Virus-2 in the Hazel Dormouse.

The hazel dormouse (Muscardinus avellanarius) population in the UK continues to decline due to habitat loss, despite reintroductions of captive-bred individuals being conducted nationally for over 30 years. Disease surveillance of captive-bred and wild dormice is performed to identify novel and existing disease threats which could impact populations. In this study, we firstly investigated cause of death in seven hazel dormice found dead in England, through next-generation sequencing identifying a virus closely related to a wood mouse encephalomyocarditis virus-2 (EMCV-2). Subsequently, lung tissue samples from 35 out of 44 hazel dormice tested positive for EMCV-2 RNA using a reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Sanger sequencing methods developed in this study. Formalin-fixed tissues available for nine hazel dormice which tested positive for EMCV-2 RNA were examined microscopically. Three cases showed moderate interstitial pneumonia with minimal to mild lymphoplasmacytic myocarditis, but no evidence of encephalitis. However, the presence of possible alternative causes of death in these cases means that the lesions cannot be definitively attributed to EMCV-2. Here, we report the first detection of EMCV-2 in hazel dormice and conclude that EMCV-2 is likely to be endemic in the hazel dormouse population in England and may be associated with clinical disease.