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Smoking is a major risk factor for many chronic diseases. Nearly all studies collecting smoking data use self-reports, which are very rarely validated. We identified 15,182 adults 18 years or older in the Third National Health and Nutrition Examination Survey. Denying smoking, the main outcome, was defined as cotinine-determined smokers self-reporting non-smoking. Multiple logistic regression modeling took into account the complex survey design and sample weights. Age and race/ethnicity-gender categories predicted denying smoking. Smokers denying smoking ranged from 0.0% for elderly (75 years and older) Mexican-American women to 67.8% for elderly non-Hispanic Black women. Among elderly smokers, non-Hispanic Black women were more likely to deny smoking than both non-Hispanic White women (odds ratio (OR) = 8.9, 95% confidence interval (CI): 2.1-38.3) and non-Hispanic Black men (OR=21.4 95% CI: 4.3-107.2). This U.S. population-based study of age-specific race/ethnicity-gender predictors of denying smoking suggests caution in interpreting smoking-related survey data. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic kidney disease, undiagnosed in a significant number of adults, is a public health problem. Given the systemic inflammatory response to periodontal disease, we hypothesized that periodontal disease could be associated with chronic kidney disease. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: We identified 12,947 adults 18 years or older with information for kidney function and at least one risk factor in the Third National Health and Nutrition Examination Survey. PREDICTOR: The main predictor was periodontal status. Other nontraditional and traditional risk factors included socioeconomic status, health status, health behavior, biomarker levels, anthropometric assessment, and health care utilization. OUTCOMES & MEASUREMENTS: Chronic kidney disease was defined using the Kidney Disease Outcomes Quality Initiative stages 3 and 4 with a moderate to severe decrease in kidney function (glomerular filtration rate, 15 to 59 mL/min/1.73 m(2)). Univariable and multivariable logistic regression models assessed the associations between chronic kidney disease and periodontal disease and other nontraditional risk factors. RESULTS: Chronic kidney disease prevalence was 3.6%; periodontal disease prevalence was 6.0%; and edentulism prevalence was 10.5%. Adults with periodontal disease and edentulous adults were twice as likely to have chronic kidney disease (adjusted odds ratio, 1.60; 95% confidence interval, 1.16 to 2.21; adjusted odds ratio, 1.85; 95% confidence interval, 1.34 to 2.56, respectively) after simultaneously adjusting for other traditional and nontraditional risk factors. LIMITATIONS: Temporal association is unknown. CONCLUSIONS: Periodontal disease and its severe consequence, edentulism, were independently associated with chronic kidney disease after adjusting for other traditional and nontraditional risk factors. This model could contribute to identifying individuals at risk of chronic kidney disease and reduce its burden. Copyright © 2008 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Trends in periodontal diseases in the USA have been documented for years. However, the results have been mixed, mostly due to different periodontal assessment protocols. This study examined change in the prevalence of periodontitis between the NHANES III and the NHANES 1999-2000, and differences in the prevalence of periodontitis among racial/ethnic groups in the USA. Analysis was limited to non-Hispanic black, non-Hispanic white, and Mexican-American adults aged 18+ yrs in the NHANES III (n=12,088) or the NHANES 1999-2000 (n=3214). The prevalences of periodontitis for the NHANES III and the NHANES 1999-2000 were 7.3% and 4.2%, respectively. In multivariable analyses, blacks were 1.88 times (95%CI: 1.42, 2.50) more likely to have periodontitis than whites surveyed in the NHANES III. However, the odds of periodontitis for blacks and Mexican-Americans did not differ from those for whites surveyed in the NHANES 1999-2000. Our findings indicate that the prevalence of periodontitis has decreased between the NHANES III and the NHANES 1999-2000 for all racial/ethnic groups in the USA. [ABSTRACT FROM AUTHOR]

The effect of oral nafazatrom (Bay g6575, 2 × 3 g) or placebo on inhaled antigen challenge was assessed in a double-blind study. In four subjects antigen challenge resulted in an immediate fall of 93.2 +/− 3.36% in airflow at 40% of vital capacity (Vp40) and a 45.85 +/− 4.95% reduction in forced partial expiratory volume at one second (FEV1). Neither nafazatrom nor placebo had any effect on baseline lung function or that after challenge. Leukotriene B4 was generated by ex vivo stimulus of blood with ionophore A23187, and quantified by high performance liquid chromatography (h.p.l.c.)-radioimmunoassay. No inhibition of LTB4 formation occurred ex vivo following oral nafazatrom, although addition of 10(-5) M nafazatrom to blood in vitro significantly inhibited LTB4 release. Peak plasma nafazatrom levels during the study ranged from 3.3 × 10(-7) M to 1.47 × 10(-6) M which are below the concentration (10(-5) M) at which significant 5- lipoxygenase inhibition occurs in vitro. Oral nafazatrom is ineffective as a 5-lipoxygenase inhibitor in man, probably because of poor bioavailability after administration. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We assessed the prevalences of periodontitis by education and income levels among US adults with data from the third National Health and Nutrition Examination Survey. METHODS: The study was limited to non-Hispanic Blacks, Mexican Americans, and non-Hispanic Whites 50 years of age or older with a complete periodontal assessment during the dental examination. RESULTS: Blacks with higher education and income levels had a significantly higher prevalence of periodontitis than their White and Mexican-American counterparts. The relationship between income level and periodontitis was modified by race/ethnicity. High-income Blacks exhibited a higher prevalence of periodontitis than did low-income Blacks and high-income Whites. CONCLUSIONS: Our findings call attention to the importance of recognizing socioeconomic status-related health differences across racial/ethnic groups within the social, political, and historical context. [ABSTRACT FROM AUTHOR]

Purpose: Both diabetes and periodontal disease are common chronic diseases. It has been established that diabetes adversely affects periodontal health. Evidence is also increasing to support treating periodontal infection to improve glycemic control in people with diabetes. This evidence comes from reports of intervention studies evaluating the effect of treating patients with varying periodontitis severity in controlled settings. Reports on the relationship between frequency of dental prophylaxis and glycemic control are sparse. The purpose of this analysis was to test the hypothesis that people who report more frequent or more recent dental prophylaxes are more likely to have better glycemic control.Methods and Materials: We analyzed screening data from 240 university hospital clinic and HMO subjects with type 2 diabetes, who were recruited for an ongoing clinical trial to investigate whether recency of dental prophylaxis appointments was associated with glycemic control as measured by level of hemoglobin A1c (HbA1c). Bivariable analysis and multiple regression modeling were conducted to evaluate associations of HbA1c with continuous and categorical variables collected from interviews and clinical examinations. The primary explanatory variables of interest were responses to interview questions on time elapsed since dental prophylaxis appointments.Results: In bivariable analysis of numerous demographic, medical, and behavioral variables, only oral diabetes medication/insulin usage status (P = .03) and doctor-recommended frequency of checking blood glucose levels (P < .01) showed statistically significant associations with HbA1c. Results from multiple regression modeling indicated that race/ethnicity, education level, and doctor-recommended frequency of checking blood glucose levels were significant predictors (P < .05), while diastolic blood pressure, low activity level, and current tobacco use were marginally non-significant predictors (P > .05). Time elapsed since dental prophylaxis appointments showed a positive but statistically non-significant association with HbA1c in both bivariable (P > .25) and regression analysis (P = .2).Conclusion: Further, more rigorous investigation of predictors of HbA1c is needed to determine if recency and frequency of dental prophylaxis contribute to glycemic control in subjects with diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Fish oil has anti-inflammatory actions that may benefit periodontal health. We investigated the longitudinal relation between dietary ω-3 fatty acids (FAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) to periodontal disease in community-dwelling elderly. Methods: Fifty-five participants aged 74 y were randomly selected from a longitudinal interdisciplinary study of aging. Dietary intake data were obtained by a 3-d weighed food intake. The dietary intakes of energy, DHA, and EPA were calculated based on the Standard Food Composition Tables in Japan. Dental examinations were carried out at baseline and once a year for 5 y. The number of teeth with periodontal progression over 5 y per person was calculated as “periodontal disease events.” Negative binomial regression analysis was conducted, which included DHA, EPA, and other covariates as independent variables to estimate the influence on periodontal disease events. Longitudinal data were analyzed for participants for whom data were available for 5 y (n =36). Results: Low DHA intake was significantly associated with more periodontal disease events. The mean number of periodontal disease events for participants who consumed the lowest tertile of DHA was approximately 1.5 times larger (lowest tertile, incidence rate ratio 1.49, 95% confidence interval 1.01–2.21) than the reference group (highest tertile of DHA consumption), after simultaneously adjusting for possible confounders. Conclusion: The findings suggest there may be an inverse, independent relation of dietary DHA intake to the progression of periodontal disease in older people. [ABSTRACT FROM AUTHOR]

Background: Proteomics is routinely used to type clinical amyloid deposits, and offers additional benefit of identifying genetic variants, which can be diagnostically useful. Reviewing the proteomics data for ATTR patients attending our Centre revealed an unusually large number of samples containing a rare pathogenic H90D TTR variant alongside the more common H90N variant., Methods: These findings raised questions to their source. Proteomics was used to monitor the generation of H90D/H90N variants in fresh, frozen, stored samples during extraction and digestion, and also following Cu 2+ -mediated oxidation., Results: There was no evidence that the variants were present in the circulation, except in one patient with genetically confirmed H90D TTR, in fresh fat aspirates or tissues from an ATTR amyloid mouse model. The variant could be generated in vitro from both wild-type TTR and ex vivo ATTR fibrils by non-enzymic oxidation of histidine at position 90. These data suggest that the H90D variant can be generated artefactually from wild-type 90H TTR through a radical-mediated oxidation of histidine, followed by its conversion to asparagine and aspartic acid. This probably occurs during storage., Conclusions: In the absence of genetic data, the identification of H90D TTR in stored tissue by proteomics should be treated with caution.

Traditional medical artificial intelligence models that are approved for clinical use restrict themselves to single-modal data ( e.g ., images only), limiting their applicability in the complex, multimodal environment of medical diagnosis and treatment. Multimodal transformer models in health care can effectively process and interpret diverse data forms, such as text, images, and structured data. They have demonstrated impressive performance on standard benchmarks, like United States Medical Licensing Examination question banks, and continue to improve with scale. However, the adoption of these advanced artificial intelligence models is not without challenges. While multimodal deep learning models like transformers offer promising advancements in health care, their integration requires careful consideration of the accompanying ethical and environmental challenges., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

DNA-based identification is vital for classifying biological specimens, yet methods to quantify the uncertainty of sequence-based taxonomic assignments are scarce. Challenges arise from noisy reference databases, including mislabelled entries and missing taxa. PROTAX addresses these issues with a probabilistic approach to taxonomic classification, advancing on methods that rely solely on sequence similarity. It provides calibrated probabilistic assignments to a partially populated taxonomic hierarchy, accounting for taxa that lack references and incorrect taxonomic annotation. While effective on smaller scales, global application of PROTAX necessitates substantially larger reference libraries, a goal previously hindered by computational barriers. We introduce PROTAX-GPU, a scalable algorithm capable of leveraging the global Barcode of Life Data System (>14 million specimens) as a reference database. Using graphics processing units (GPU) to accelerate similarity and nearest-neighbour operations and the JAX library for Python integration, we achieve over a 1000 × speedup compared with the central processing unit (CPU)-based implementation without compromising PROTAX's key benefits. PROTAX-GPU marks a significant stride towards real-time DNA barcoding, enabling quicker and more efficient species identification in environmental assessments. This capability opens up new avenues for real-time monitoring and analysis of biodiversity, advancing our ability to understand and respond to ecological dynamics. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

This study looked at using modified camelina oil to develop sustainable coatings that could replace those derived from petroleum-based materials for use in packaging and other industrial sectors. Solvent-free synthesis of maleic anhydride grafted camelina oil (MCO) was carried out at two different temperatures (200 and 230 °C) to obtain sustainable hydrophobic coating materials for paper substrates. Maleic anhydride grafting of camelina oil was confirmed with attenuated total reflectance-Fourier transform infrared and NMR spectroscopic techniques, and up to 16% grafting of maleic anhydride was achieved, as determined by the titration method. MCO, obtained at different reaction temperatures, was coated onto cellulosic paper and evaluated for its hydrophobicity, mechanical, oxygen, and water vapor barrier properties. Scanning electron microscopy indicated the homogeneous dispersion of coating material onto the paper substrate. MCO-coated papers (MCO-200C paper and MCO-230C paper) provided a water contact angle of above 90° which indicates that the modified oil was working as a hydrophobic coating. Water vapor permeability (WVP) testing of coated papers revealed a reduction in WVP of up to 94% in comparison to the uncoated paper. Moreover, an improved oxygen barrier property was also observed for paper coated with both types of MCO. Analysis of the mechanical properties showed a greater than 70% retention of tensile strength and up to a five-fold increase in elongation at break of coated versus uncoated papers. Overall, the results show that camelina oil, a renewable resource, can be modified to produce environmentally friendly hydrophobic coating materials with improved mechanical and water vapor barrier properties that can serve as a potential coating material in the packaging industry. The results of this research could find applications in the huge paper packaging industries, specially in food packaging., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Racial disparities in the prevalence of periodontal disease are consistent and persistent. The epidemiology of periodontal disease demonstrates racial inequities: non-Hispanic Black (14.7%), Mexican American (13.4%), and other Hispanic adults (7.8%) experience a higher prevalence of severe periodontal disease than non-Hispanic White adults (5.9%). Epidemiologic and clinical research on periodontal health suffers from the same problem that has plagued the health equity movement, an over emphasis on describing racial inequities coupled with few interventions that reduce racial health inequity. Over the decades that racial inequities in periodontal disease have been observed, many have argued that systemic racism is the fundamental driver of racial health inequity. This paper interrogates the roles of systemic racism, dental education, clinical treatment, and patient behavior in periodontal disease. We describe how, together, these mechanisms contribute to racial disparities in periodontal outcomes. However, it is insufficient for oral health equity scientists to only describe and discuss the negative effects of systemic racism. The imperative is to create antiracist strategies designed to eliminate systemic racism. Health equity scientists must also specify how dental systems operate in a racist manner and create effective clinical strategies designed to reduce racial disparities in periodontal disease., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The mechanism that converts native human transthyretin into amyloid fibrils in vivo is still a debated and controversial issue. Commonly, non-physiological conditions of pH, temperature, or organic solvents are used in in vitro models of fibrillogenesis of globular proteins. Transthyretin amyloid formation can be achieved under physiological conditions through a mechano-enzymatic mechanism involving specific serine proteases such as trypsin or plasmin. Here, we investigate S52P and L111M transthyretin variants, both causing a severe form of systemic amyloidosis mostly targeting the heart at a relatively young age with heterogeneous phenotype among patients. Our studies on thermodynamics show that both proteins are significantly less stable than other amyloidogenic variants. However, despite a similar thermodynamic stability, L111M variant seems to have enhanced susceptibility to cleavage and a lower tendency to form fibrils than S52P in the presence of specific proteases and biomechanical forces. Heparin strongly enhances the fibrillogenic capacity of L111M transthyretin, but has no effect on the S52P variant. Fibrillar seeds similarly affect the fibrillogenesis of both proteins, with a stronger effect on the L111M variant. According to our model of mechano-enzymatic fibrillogenesis, both full-length and truncated monomers, released after the first cleavage, can enter into fibrillogenesis or degradation pathways. Our findings show that the kinetics of the two processes can be affected by several factors, such as intrinsic amyloidogenicity due to the specific mutations, environmental factors including heparin and fibrillar seeds that significantly accelerate the fibrillogenic pathway., (© 2024 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Objective: A scoping review of studies published in the first year of the COVID-19 pandemic focused on individuals with pre-existing symptoms of depression, anxiety, and specified stressor-related disorders, with the objective of mapping the research conducted., Eligibility Criteria: (1) direct study of individuals with pre-existing depressive, anxiety, and/or specified stressor-related (i.e., posttraumatic stress, acute stress) disorders/issues; (2) focus on mental health-related pandemic effects, and; (3) direct study of mental health symptoms related to depression, anxiety, or psychological distress., Sources of Evidence: Database-specific subject headings and natural language keywords were searched in Medline, Embase, APA PsycInfo, and Cumulative Index to Nursing & Allied Health Literature (CINAHL) up to March 3, 2021. Review of potentially relevant studies was conducted by two independent reviewers and proceeded in two stages: (1) title and abstract review, and; (2) full paper review., Data Charting: Study details (i.e., location, design and methodology, sample or population, outcome measures, and key findings) were extracted from included studies by one reviewer and confirmed by the Principal Investigator., Results: 66 relevant articles from 26 countries were identified. Most studies adopted a cross-sectional design and were conducted via online survey. About half relied on general population samples, with the remainder assessing special populations, primarily mental health patients. The most commonly reported pre-existing category of disorders or symptoms was depression, followed closely by anxiety. Most studies included depressive and anxiety symptoms as outcome measures and demonstrated increased vulnerability to mental health symptoms among individuals with a pre-existing mental health issue., Conclusion: These findings suggest that improved mental health supports are needed during the pandemic and point to future research needs, including reviews of other diagnostic categories and reviews of research published in subsequent years of the pandemic., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wickens et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Deep learning for computer vision has shown promising results in the field of entomology, however, there still remains untapped potential. Deep learning performance is enabled primarily by large quantities of annotated data which, outside of rare circumstances, are limited in ecological studies. Currently, to utilize deep learning systems, ecologists undergo extensive data collection efforts, or limit their problem to niche tasks. These solutions do not scale to region agnostic models. However, there are solutions that employ data augmentation, simulators, generative models, and self-supervised learning that can supplement limited labelled data. Here, we highlight the success of deep learning for computer vision within entomology, discuss data collection efforts, provide methodologies for optimizing learning from limited annotations, and conclude with practical guidelines for how to achieve a foundation model for entomology capable of accessible automated ecological monitoring on a global scale., (© 2023 The Authors. Ecology Letters published by John Wiley & Sons Ltd.)

Objectives: The COVID-19 pandemic has tremendously impacted the U.S. healthcare system, but no study has examined the impact of the pandemic on utilization of dental care among U.S. children. Changes in past-year dental versus medical visits and perceived unmet health needs between 2019 and 2020 among U.S. children aged 1-17 years were examined., Methods: National and state representative, cross-sectional data from the National Survey of Children's Health conducted during June 2019-January 2020 (i.e. pre-pandemic, n = 28 500) and July 2020-January 2021 (i.e. intra-pandemic, n = 41 380) were analysed. Any past-year visit and perceived unmet needs (i.e. delay or inability to receive needed care) were reported by the parent proxy. Weighted prevalence estimates were compared using two-tailed chi-squared tests at p < .05. Poisson regression analyses were used to explore the relationship between having dental and/or medical unmet needs during the pandemic and indicators of poor health and social wellbeing., Results: Between 2019 and 2020, a significantly reduced prevalence of past-year medical (87.2%-81.3%) and dental visits (82.6%-78.2%) among U.S. children aged 1-17 years (all p < .05) were observed. Correspondingly, perceived unmet needs increased by half for dental care (from 2.9% in 2019 to 4.4% in 2020) and almost one-third for medical care (from 3.2% to 4.2% in 2020). Subgroups with the highest prevalence of unmet dental need included those with low socio-economic status, living with their grandparents, uninsured and living with a smoker., Conclusions: Unmet health needs increased in general but increased more for dental than for medical care among U.S. children aged 1-17 years. Enhanced and sustained efforts will be needed to deliver targeted services towards disadvantaged segments of the population to narrow existing disparities., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The plasma protein transthyretin (TTR), a transporter for thyroid hormones and retinol in plasma and cerebrospinal fluid, is responsible for the second most common type of systemic (ATTR) amyloidosis either in its wild type form or as a result of destabilizing genetic mutations that increase its aggregation propensity. The association between free calcium ions (Ca 2+ ) and TTR is still debated, although recent work seems to suggest that calcium induces structural destabilization of TTR and promotes its aggregation at non-physiological low pH in vitro. We apply high-resolution NMR spectroscopy to investigate calcium binding to TTR showing the formation of labile interactions, which leave the native structure of TTR substantially unaltered. The effect of calcium binding on TTR-enhanced aggregation is also assessed at physiological pH through the mechano-enzymatic mechanism. Our results indicate that, even if the binding is weak, about 7% of TTR is likely to be Ca 2+ -bound in vivo and therefore more aggregation prone as we have shown that this interaction is able to increase the protein susceptibility to the proteolytic cleavage that leads to aggregation at physiological pH. These events, even if involving a minority of circulating TTR, may be relevant for ATTR, a pathology that takes several decades to develop.

The globular to fibrillar transition of proteins represents a key pathogenic event in the development of amyloid diseases. Although systemic amyloidoses share the common characteristic of amyloid deposition in the extracellular matrix, they are clinically heterogeneous as the affected organs may vary. The observation that precursors of amyloid fibrils derived from circulating globular plasma proteins led to huge efforts in trying to elucidate the structural events determining the protein metamorphosis from their globular to fibrillar state. Whereas the process of metamorphosis has inspired poets and writers from Ovid to Kafka, protein metamorphism is a more recent concept. It is an ideal metaphor in biochemistry for studying the protein folding paradigm and investigating determinants of folding dynamics. Although we have learned how to transform both normal and pathogenic globular proteins into fibrillar polymers in vitro , the events occurring in vivo , are far more complex and yet to be explained. A major gap still exists between in vivo and in vitro models of fibrillogenesis as the biological complexity of the disease in living organisms cannot be reproduced at the same extent in the test tube. Reviewing the major scientific attempts to monitor the amyloidogenic metamorphosis of globular proteins in systems of increasing complexity, from cell culture to human tissues, may help to bridge the gap between the experimental models and the actual pathological events in patients., Competing Interests: For sake of clarity, we would like to disclose the following: research grant (2021–2023) from Pfizer (DC and VB); speaker and consulting honoraria from Alnylam, Pfizer, Akcea and SOBI (LO); participation to advisory boards for Pfizer, Alnylam Pharmaceuticals Inc. (VB and JG) and Eidos, Ionis, Intellia (JG). VB, GT, and PM are authors of a patent for ATTR amyloidosis agents. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Faravelli, Mondani, Mangione, Raimondi, Marchese, Lavatelli, Stoppini, Corazza, Canetti, Verona, Obici, Taylor, Gillmore, Giorgetti and Bellotti.)

The artificial intelligence revolution has been spurred forward by the availability of large-scale datasets. In contrast, the paucity of large-scale medical datasets hinders the application of machine learning in healthcare. The lack of publicly available multi-centric and diverse datasets mainly stems from confidentiality and privacy concerns around sharing medical data. To demonstrate a feasible path forward in medical image imaging, we conduct a case study of applying a differentially private federated learning framework for analysis of histopathology images, the largest and perhaps most complex medical images. We study the effects of IID and non-IID distributions along with the number of healthcare providers, i.e., hospitals and clinics, and the individual dataset sizes, using The Cancer Genome Atlas (TCGA) dataset, a public repository, to simulate a distributed environment. We empirically compare the performance of private, distributed training to conventional training and demonstrate that distributed training can achieve similar performance with strong privacy guarantees. We also study the effect of different source domains for histopathology images by evaluating the performance using external validation. Our work indicates that differentially private federated learning is a viable and reliable framework for the collaborative development of machine learning models in medical image analysis., (© 2022. The Author(s).)

Cardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTR S52P . The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α 2 -antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments., (© 2021. The Author(s).)

Apolipoprotein A-IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA-IV amyloidosis was identified in 16 patients attending the National Amyloidosis Centre and in eight clinical samples received for histology review. Unexpectedly, proteomics identified the presence of ApoA-IV signal sequence residues (p.18-43 to p.20-43) in 16/24 trypsin-digested amyloid deposits but in only 1/266 non-ApoA-IV amyloid samples examined. These additional signal residues were also detected in the cardiac sample from the Swedish patient in which ApoA-IV amyloid was first described, and in plasma from a single cardiac ApoA-IV amyloidosis patient. The most common signal-containing peptide observed in ApoA-IV amyloid, p.20-43, and to a far lesser extent the N-terminal peptide, p.21-43, were fibrillogenic in vitro at physiological pH, generating Congo red-positive fibrils. The addition of a single signal-derived alanine residue to the N-terminus has resulted in markedly increased fibrillogenesis. If this effect translates to the mature circulating protein in vivo, then the presence of signal may result in preferential deposition as amyloid, perhaps acting as seed for the main circulating native form of the protein; it may also influence other ApoA-IV-associated pathologies. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland., (© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.)

Objective: This systematic review assesses the association of tooth loss (TL), as the exposure, with morbidity and mortality by diabetes mellitus (DM) status, as the outcome, in older adults., Background: Individuals with DM have higher prevalence of severe TL and increased risk of developing morbidities and mortality. No systematic review has evaluated the association between TL with morbidity and mortality by DM status., Material and Methods: Comprehensive searches used multiple publication databases containing reports published between 01/01/2000 and 04/21/2021. Two authors independently evaluated included studies for quality and risk of bias using the Critical Appraisal Skills Programme (CASP) checklist for cohort and Center for Evidence-Based Medicine (CEBM) critical appraisal sheet for cross-sectional studies, while a third author arbitrated decisions to resolve disagreements., Results: Thirteen studies met the inclusion criteria: eight cross-sectional and five cohort. Qualitative review of the included studies indicated TL is associated with increased incidence and prevalence of DM. TL is also associated with DM-related morbidities including greater prevalence of heart disease, diabetic retinopathy, metabolic syndrome; poorer health-related quality of life; poorer survival of participants with chronic kidney disease; and increased medical expenditure. Overall, the quality of the evidence reviewed was medium, as per the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence., Conclusions/practical Implications: This review found significant associations of TL with prevalence and incidence of DM and adverse DM-related outcomes. An interprofessional team-care approach that includes an oral health component could benefit the prevention and management of DM., (© 2021. The Author(s).)

Despite many reported associations, the direct cause of neurodegeneration responsible for cognitive loss in Alzheimer's disease and some other common dementias is not known. The normal human plasma protein, serum amyloid P component, a constituent of all human fibrillar amyloid deposits and present on most neurofibrillary tangles, is cytotoxic for cerebral neurones in vitro and in experimental animals in vivo . The neocortical content of serum amyloid P component was immunoassayed in 157 subjects aged 65 or more with known dementia status at death, in the large scale, population-representative, brain donor cohort of the Cognitive Function and Ageing Study, which avoids the biases inherent in studies of predefined clinico-pathological groups. The serum amyloid P component values were significantly higher in individuals with dementia, independent of serum albumin content measured as a control for plasma in the cortex samples. The odds ratio for dementia at death in the high serum amyloid P component tertile was 5.24 (95% confidence interval 1.79-15.29) and was independent of Braak tangle stages and Thal amyloid-β phases of neuropathological severity. The strong and specific association of higher brain content of serum amyloid P component with dementia, independent of neuropathology, is consistent with a pathogenetic role in dementia., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)