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Background Recently, injectable cabotegravir/rilpivirine (ICAB/RPV) became available for HIV treatment. However, there are no real-life data on the impact of switching to ICAB/RPV on sleep disturbances (SD). Therefore, we aimed at assessing and investigating this aspect in our cohort. Methods A SD multidimensional assessment (Epworth Sleepiness scale, Insomnia severity Index, Berlin Questionnaire, and Pittsburg Sleep Quality Index, PSQI) was performed to all people who consented before starting ICAB/RPV and 12 wk after the switch. Demographics, life-style habits, laboratory, and clinical data were collected from medical health records. Results To June 2023, 46 people were included, 76.1% males, with a median age of 48.5 (IQR: 41–57), 50% had multimorbidity, 13% was on polypharmacy. Median age with HIV and CD4 + T cell count nadir were 10 (5–19.5) years and 360 (205–500) cell/mm3, respectively. The reason to start a long-acting strategy was person’s choice in all cases. Baseline antiretroviral regimens were mostly: tenofovir alafenamide/emtricitabine/rilpivirine (39.1%) and dolutegravir/lamivudine (32.6%). No significant changes were observed in any of the scores for each questionnaire, but for a worsening PSQI. 37% people reported a subjectively improved sleep quality, even if statistically significant changes were not observed in almost all the sleep parameters. Conclusions To the best of our knowledge, this is the first study exploring impact of switching to ICAB/RPV on SD. Despite integrase inhibitor have been associated with SD, we did not observed a negative impact on sleep quality after the switch to ICAB/RPV. More studies and with larger number of people are necessary to confirm our results.

Neste artigo, tem-se por objetivo analisar as questões presentes nas três edições da Prova Paraná aplicadas no ano letivo de 2023. Para tanto, foram inventariadas as provas cujos arquivos estavam disponíveis eletronicamente, com exceção da prova da 2ª edição do 8º ano, e categorizaram-se as questões de acordo com seu nível de demanda cognitiva (reprodução, conexão ou reflexão), seu tipo de contexto (real, realista, puramente matemático ou fantasioso) e sua ordem do contexto (bare problem, ordem zero, primeira ordem, segunda ordem ou terceira ordem). Observaram-se uma predominância de questões de baixa demanda cognitiva, falta de questões de reflexão, limitações nos tipos de contexto, predomínio de questões de primeira ordem e falhas na abordagem da prova como diagnóstico.

Introdução: Cargas virais do SARS-CoV-2 elevadas e mantidas em secreções respiratórias parecem estar relacionadas a gravidade da COVID-19. No entanto, alguns autores observaram elevada carga viral mesmo em pessoas assintomáticas. Diversos fatores podem estar implicados como maior inóculo na transmissão, menor controle de replicação, menor resposta ao tratamento. Assim, são necessários estudos da influência da dinâmica de secreção viral em secreções respiratórias na letalidade por COVID-19. Objetivo: Avaliar a associação entre a evolução da carga viral do SARS-CoV-2 em secreções respiratórias e o prognostico da Síndrome Respiratória Aguda Grave (SRAG) por COVID-19, em termos de necessidade de ventilação mecânica não invasiva (VMNI), de ventilação mecânica invasiva (VMI), ou de evolução para óbito ou para desenvolvimento de sequelas, e seus fatores associados. Método: Estudo de coortes. Exposição: carga viral do SARS-CoV-19 estimada pelo método ΔCt; desfecho: VMNI, VMI, sequela cardíaca ou pulmonar, alta/óbito. Participaram do estudo indivíduos adultos (idade ≥18 anos) internados por SRAG por SARS-CoV-2. Realizado questionário padronizado com informações demográficas, epidemiológicas, clínicas, virológicas, laboratoriais e de imagem, de necessidade de suporte, e de tratamento, no programa RedCap. Os pacientes eram reavaliados em mais quatro ocasiões com novos RT-PCR para SARS-CoV-2 em secreção de nasofaringe (48-72h, 6-8 dias, 10-15 dias, 20-25 dias). Avaliada a evolução com VMNI ou VMNI, alta/óbito hospitalar, sequelas pulmonares e cardiovasculares, além da produção de anticorpos neutralizantes (AN). Resultados: Entre 10/2020 e 11/2021, foram inclusos 23 pacientes com SRAG por SARS-CoV-2. Metade dos pacientes necessitaram suporte de O2 com máscara com reservatório e 26,1% foram submetidos a VMI. Dois pacientes evoluiram com o óbito. A carga viral do SARS-CoV-2 por ΔCt em swab de naso/orofaringe se manteve elevada (> 10) após 7d de internação em pacientes que evoluiram com óbito. Fatores associados ao óbito na admissão foram idade > 60 anos, hipotermia, bradicardia, hipotensão, alterações ECG (alargamento da onda p e BAV de 1 grau), contagem neutrófilos < 5000 células/mm3, D-dímero > 1 mg/L; PCR < 10 mg/dL e bilirrubina total < 0,4 mg/dL. Os dois pacientes que evoluíram com o óbito não receberam corticoide nas primeiras 72h de internação. > 95% dos pacientes evoluíram com produção de AN após a doença (mediana de 99,3%). Conclusão: A manutenção de carga viral elevada após uma semana parece associada à letalidade.

BackgroundSeronegative autoimmune hepatitis in children is a rare but potentially severe disease, sometimes requiring liver transplantation. This type of hepatitis may be associated with various immunological and hematological disorders, ranging from isolated lymphopenia to aplastic anemia. Precise pathophysiological mechanisms are still unknown, but the role of viruses cannot be excluded, either as directly pathogenic or as triggers, responsible for an inappropriate immune stimulation. Having the impression of an increasing number of seronegative autoimmune hepatitis since the beginning of SARS-CoV-2 pandemia period, we hypothesized that SARS-CoV-2 virus could be an infectious trigger.MethodsWe conducted a retrospective, observational, descriptive study about children with seronegative autoimmune hepatitis, in a tertiary care center, between 2010 and 2022.ResultsThirty-two patients were included. The overall incidence of seronegative autoimmune hepatitis increased 3.3-fold in 2020-2022, during the SARS-CoV-2 pandemia period (16 patients in 2.8 years) compared with 2010-2019 the pre pandemia period (16 patients in 9 years). Patients’ clinical and biochemical liver characteristics did not differ between the two periods. Hematological damages were less severe during the pandemia period. Immunological studies revealed a dysregulated immune response. The initiation of immunosuppressive therapy (corticosteroids ± cyclosporine) was earlier during the pandemia period than before.ConclusionIn cases of undetermined acute hepatitis, an immune-mediated origin should be considered, prompting a liver biopsy. If the histological aspect points to an immune origin, immunosuppressive treatment should be instituted even though autoimmune hepatitis antibodies are negative. Close hematological monitoring must be performed in all cases. The 3.3-fold increase of cases during the SARS-CoV-2 pandemia will need to be further analyzed to better understand the underlying immunological mechanisms, and to prove its potential involvement.

Aims: To determine whether discrete lipid profiles (refer to as lipid phenotyping) can be used to stratify cardiovascular risk in individuals with type 2 diabetes. Methods and results: Cardiovascular Health Study participants with diabetes and fasting lipid profiles at baseline (n = 866) were categorized separately by level of LDL cholesterol and HDL-C/Triglyceride (Tg) profiles (low Tg/high HDL-C; high Tg/low HDL-C; high Tg only or low HDL-C only). We performed Cox multivariate regression analysis to assess the risk of CVD mortality, incident myocardial infarction (MI), heart failure (HF), stroke, and composite MACE (MI, HF, stroke, and CVD mortality) associated with each lipid category. We also calculated risk estimates for MACE using lipid measures as continuous variables. In the fully adjusted model, the high triglyceride plus low HDL-C cholesterol phenotype demonstrated risk that was at least as high as the highest LDL-C sub-group phenotype for CVD mortality (Hazard ratio {HR} 1.58 vs 1.48), MI (HR 1.53 vs 1.58), HF (HR 1.47 vs 1.20), stroke (HR 2.02 vs 1.43), and MACE (HR 1.58 vs 1.38). When modeled continuously, the HR per SD for MACE was 1.12 (p = 0.03) for LDL-C and 1.19–1.20 (p < 0.001) for triglycerides or remnant cholesterol. Conclusions: Participants with the high triglyceride/low HDL-C phenotype had equivalent or higher CVD risk than those with the high LDL-C phenotype. Further studies are necessary to determine whether lipid phenotyping accounts for the substantial CVD risk not explained by LDL cholesterol among individuals with type 2 diabetes.

This study adopts a new approach describing palaeohydrology and palaeoclimates based on the interpretation of stable oxygen isotopes (δ18Op) recorded in fossil crocodilian teeth. They represent an archive of prime interest for tracking freshwater palaeoenvironmental change, applicable to many palaeontological localities in the world: crocodilian teeth are abundant in continental basins and have been widely distributed since their diversification during the Mesozoic; the enamel phosphate is resistant to diagenesis and retains its original isotopic composition over geological timescales; and their δ18Op mainly relies on that of the crocodilian's home waterbody (δ18Ow), which in turn reflects waterbody types, regional climate, and evaporation conditions. This study presents the first application of this theoretical interpretative model to the Shungura Formation (Lower Omo Valley, Ethiopia), a key witness of the important environmental change in eastern Africa during the Plio-Pleistocene that impacted the evolution of regional faunas, including humans. In this complex and variable environmental context, the δ18Op of coexisting crocodilians allows for the fingerprinting of the diversity of aquatic environments they had access to at a local scale. This study sheds light on two important results: the δ18Op of crocodilian teeth (1) indicates stable aquatic environments in the northern Turkana Depression from 2.97 to ca. 2.57 Ma but a decline in local waterbodies diversity after 2.32 Ma, suggesting increasing aridity, and (2) shows, like previous geochemical studies on palaeosols and bivalves in the area, a significant increase in δ18Ow from 2.97 to ca. 1.14 Ma, likely due to the shifting air stream convergence zones between the West African and Indian Summer Monsoons and/or reduced rainfall over the Ethiopian Highlands.

Background: The introduction of rapid antigen tests revolutionized the approach to SARS-CoV-2 diagnosis, offering prompt and accurate results with high sensitivity and specificity. Although it is more cost- and time-saving than the gold standard, real-time polymerase chain reaction (RT-PCR), the efficacy in general population screening in both hospital- and community-based settings remains unknown. Moreover, rapid antigen testing is limited by qualitative results. This study aims to evaluate the diagnostic reliability of the LumiraDx™ rapid antigen test during the Omicron era and to investigate its quantitative (analogue-to-digital converter (ADC)) results in comparison with RT-PCR Ct values. Methods: This prospective study included all adult patients with mild-to-moderate SARS-CoV-2 symptoms who were not hospitalised and did not require oxygen supplementation, consented to participate, and attended the Infectious and Tropical Diseases Unit of Padua University Hospital from July 14th, 2022 to January 3rd, 2023. The patients underwent two different tests simultaneously: a nasal LumiraDx™ swab and a real-time RT-PCR assay performed on a nasopharyngeal swab. Sampling was repeated several times for a subset of subjects. Results: We enrolled 266 consecutive participants and collected 601 pairs of LumiraDx™ and RT-PCR samples. The most prevalent variant was BA.4/BA.5 Omicron (60.2 %). The sensitivity and specificity of LumiraDx™ test when compared to real-time RT-PCR results as the reference standard were 93.1 % and 79.75 %, respectively. No significant differences in diagnostic reliability were found based on the available characteristics, age, sex, symptom status, or COVID-19 variant, except for the days from symptom onset. According to the multilevel logistic regression analysis, the only independent variable significantly associated with test concordance was the Ct value (adjusted odds ratio (OR) = 0.56, p

O objetivo deste trabalho foi investigar o uso do silício (Si) no crescimento e produção do feijoeiro em diferentes condições hídricas no substrato. Para isso, plantas de feijão comum, Phaseolus vulgaris, cultivar SCS207 “Querência” do grupo carioca, foram cultivadas em vasos plásticos contendo 8 dm-3 de substrato no interior da casa de vegetação do Instituto Federal Catarinense, Campus Videira. As plantas cresceram com o substrato mantido próxima a capacidade de campo por 45 dias após a emergência (DAE), quando então, foram estabelecidos dois níveis de água, definidos a partir da porosidade total do solo, com valores de 50 (D+) e 100% (D-) do volume total de poros ocupados por água (Capacidade de Campo), sendo o controle da irrigação realizado pelo método gravimétrico (pesagem diária dos vasos), adicionando-se água até que a massa do vaso atingisse o valor prévio determinado, considerando-se a massa do solo e de água. A aplicação das doses de Si foi realizada através de um pulverizador manual com capacidade de 500 mL e um bico tipo leque para aplicação. Plantas controles onde não foram aplicadas o Si, foram pulverizadas com água destilada. Utilizou-se o fertilizante foliar mineral simples silicato de potássio (Flex Silício®) nas doses: 0 mL/L (Controle, Si-) e 6 mL/L (Si+) de silicato de potássio, aplicados aos 45, 60 e 75 DAE. O experimento foi montado em esquema fatorial 2×2, com quatro repetições, composto por dois níveis de água [100 e 50% da capacidade de campo, ou seja, sem déficit hídrico (D-) e com déficit hídrico (D+), respectivamente] e dois níveis de doses do Si [0,0 mL/L (Controle, Si-) e 6mL/L (Si+), dispostos num delineamento experimental inteiramente casualizado, em parcelas subdivididas no tempo (15, 30, 45, 60, 75 e 90 DAE). Cada unidade experimental foi composta de um vaso plástico contendo duas plantas. As avaliações de crescimento e desenvolvimento foram realizadas quinzenalmente, até o final do período experimental, iniciadas após o décimo quinto dia da emergência das plântulas. Em cada coleta foram analisados por planta em cada tratamento as seguintes variáveis: altura, diâmetro do coleto, número de vagens e estimativa da área foliar, a matéria seca das folhas, ramos e haste, raiz e total (folha, ramos e haste, e raiz). A produção foi mensurada através da massa seca de vagens e das sementes (grãos) por planta, realizada no final do experimento. Também foi estimada a produtividade potencial do feijoeiro de acordo com os valores obtidos da matéria seca dos grãos por planta, considerando um espaçamento de 40 x 50 cm em um hectare (ha), o que totalizou 50 mil plantas/ha. Os resultados obtidos mostraram, de modo geral, que o fornecimento de Si beneficiou o crescimento vegetativo e o desenvolvimento das plantas, em condições de adequada disponibilidade hídrica no substrato, como pode ser evidenciado pelos aumentos significativos encontrados para a altura, diâmetro do coleto, comprimento da raiz e área foliar. O fornecimento de Si aliado a adequada disponibilidade hídrica no substrato (Si+D-) contribuiu para os incrementos significativos na matéria seca das folhas, haste e ramos, raiz e total, levando a maior produção na matéria seca de grãos e da produtividade. O Si também contribuiu para a atenuação do déficit hídrico, melhorando o crescimento e rendimento do feijoeiro quando comparado com as plantas onde não era fornecido o elemento.

Background Normalization of echocardiographic chamber measurements for body surface area may result in misclassification of individuals with obesity or sarcopenia. Normalization for alternative measures of body size may be preferable, but there remains a dearth of information on their normative values and association with cardiovascular function metrics. Methods and Results A total of 3032 individuals underwent comprehensive 2‐dimensional echocardiography at Exam 6 in MESA (Multi‐Ethnic Study of Atherosclerosis). In the subgroup of 608 individuals free of cardiopulmonary disease (69.5±7.0 years, 46% male, 48% White, 17% Chinese, 15% Black, 21% Hispanic), normative values were derived for left and right cardiac chamber measurements across a variety of ratiometric (body surface area, body mass index, height) and allometric (height1.6, height2.7) scaling parameters. Normative upper and lower reference values were provided for each scaling parameter stratified across age groups, sex, and race or ethnicity. Among scaling parameters, body surface area and height were associated with the least variability across race and ethnicity categories and height2.7 was associated with the least variability across sex categories. Conclusions In this diverse cohort of community‐dwelling older adults, we provide normative values for common echocardiographic parameters across a variety of indexation methods.

Abstract Over the past years, the development of innovative smart wound dressings is revolutionizing wound care management and research. Specifically, in the treatment of diabetic foot wounds, three-dimensional (3D) bioprinted patches may enable personalized medicine therapies. In the present work, a methacrylated hyaluronic acid (MeHA) bioink is employed to manufacture 3D printed patches to deliver small extracellular vesicles (sEVs) obtained from human mesenchymal stem cells (MSC-sEVs). The production of sEVs is maximized culturing MSCs in bioreactor. A series of in vitro analyses are carried out to demonstrate the influence of MSC-sEVs on functions of dermal fibroblasts and endothelial cells, which are the primary functional cells in skin repair process. Results demonstrate that both cell populations are able to internalize MSC-sEVs and that the exposure to sEVs stimulates proliferation and migration. In vivo experiments in a well-established diabetic mouse model of pressure ulcer confirm the regenerative properties of MSC-sEVs. The MeHA patch enhances the effectiveness of sEVs by enabling controlled release of MSC-sEVs over 7 days, which improve wound epithelialization, angiogenesis and innervation. The overall findings highlight that MSC-sEVs loading in 3D printed biomaterials represents a powerful technique, which can improve the translational potential of parental stem cell in terms of regulatory and economic impact.

Abstract Background Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ4-3-oxosteroid 5β-reductase (Δ4-3-oxo-R) deficiency. Methods Sixteen patients with Δ4-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed. Results First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1–159) and serum liver tests normalized in all within 6–12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1–24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-∆4 derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity. Conclusions Oral cholic acid therapy is a safe and effective treatment for patients with Δ4-3-oxo-R deficiency.

Glycogen storage disease type III (GSDIII) is a rare inborn error of metabolism affecting liver, skeletal muscle, and heart due to mutations of the AGL gene encoding for the glycogen debranching enzyme (GDE). No curative treatment exists for GSDIII. The 4.6 kb GDE cDNA represents the major technical challenge toward the development of a single recombinant adeno- associated virus-derived (rAAV-derived) vector gene therapy strategy. Using information on GDE structure and molecular modeling, we generated multiple truncated GDEs. Among them, an N-terminal-truncated mutant, [DELTA]Nter2-GDE, had a similar efficacy in vivo compared with the full-size enzyme. A rAAV vector expressing [DELTA]Nter2- GDE allowed significant glycogen reduction in heart and muscle of [Agl.sup.-/-] mice 3 months after i.v. injection, as well as normalization of histology features and restoration of muscle strength. Similarly, glycogen accumulation and histological features were corrected in a recently generated [Agl.sup.-/-] rat model. Finally, transduction with rAAV vectors encoding [DELTA]Nter2-GDE corrected glycogen accumulation in an in vitro human skeletal muscle cellular model of GSDIII. In conclusion, our results demonstrated the ability of a single rAAV vector expressing a functional mini-GDE transgene to correct the muscle and heart phenotype in multiple models of GSDIII, supporting its clinical translation to patients with GSDIII., Introduction Glycogen storage disease type III (GSDIII) is a rare inborn error of metabolism, with an incidence of 1 in 100,000, caused by mutations in the AGL gene, which encodes [...]

ABSTRACT Each genome encodes some codons more frequently than their synonyms (codon usage bias), but codons are also arranged more frequently into specific pairs (codon pair bias). Recoding viral genomes and yeast or bacterial genes with non-optimal codon pairs has been shown to decrease gene expression. Gene expression is thus importantly regulated not only by the use of particular codons but also by their proper juxtaposition. We therefore hypothesized that non-optimal codon pairing could likewise attenuate Mycobacterium tuberculosis (Mtb) genes. We explored the role of codon pair bias by recoding Mtb genes (rpoB, mmpL3, and ndh) and assessing their expression in the closely related and tractable model organism M. smegmatis. To our surprise, recoding caused the expression of multiple smaller protein isoforms from all three genes. We confirmed that these smaller proteins were not due to protein degradation but instead issued from new transcription initiation sites positioned within the open reading frame. New transcripts gave rise to intragenic translation initiation sites, which, in turn, led to the expression of smaller proteins. We next identified the nucleotide changes associated with these new sites of transcription and translation. Our results demonstrated that apparently benign, synonymous changes can drastically alter gene expression in mycobacteria. More generally, our work expands our understanding of the codon-level parameters that control translation and transcription initiation. IMPORTANCE Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the deadliest infectious diseases worldwide. Previous studies have established that synonymous recoding to introduce rare codon pairings can attenuate viral pathogens. We hypothesized that non-optimal codon pairing could be an effective strategy for attenuating gene expression to create a live vaccine for Mtb. We instead discovered that these synonymous changes enabled the transcription of functional mRNA that initiated in the middle of the open reading frame and from which many smaller protein products were expressed. To our knowledge, this is one of the first reports that synonymous recoding of a gene in any organism can create or induce intragenic transcription start sites.

Background & Aims: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare liver disease caused by biallelic variations in ABCB4. Data reporting on the impact of genotype and of response to ursodeoxycholic acid (UDCA) therapy on long-term outcomes are scarce. Methods: We retrospectively describe a cohort of 38 patients with PFIC3 with a median age at last follow-up of 19.5 years (range 3.8–53.8). Results: Twenty patients presented with symptoms before 1 year of age. Thirty-one patients received ursodeoxycholic acid (UDCA) therapy resulting in serum liver test improvement in 20. Twenty-seven patients had cirrhosis at a median age of 8.1 years of whom 18 received a liver transplant at a median age of 8.5 years. Patients carrying at least one missense variation were more likely to present with positive (normal or decreased) canalicular MDR3 expression in the native liver and had prolonged native liver survival (NLS; median 12.4 years [range 3.8-53.8]). In contrast, in patients with severe genotypes (no missense variation), there was no detectable canalicular MDR3 expression, symptom onset and cirrhosis occurred earlier, and all underwent liver transplantation (at a median age of 6.7 years [range 2.3–10.3]). The latter group was refractory to UDCA treatment, whereas 87% of patients with at least one missense variation displayed an improvement in liver biochemistry in response to UDCA. Biliary phospholipid levels over 6.9% of total biliary lipid levels predicted response to UDCA. Response to UDCA predicted NLS. Conclusions: Patients carrying at least one missense variation, with positive canalicular expression of MDR3 and a biliary phospholipid level over 6.9% of total biliary lipid levels were more likely to respond to UDCA and to exhibit prolonged NLS. Impact and implications: In this study, data show that genotype and response to ursodeoxycholic acid therapy predicted native liver survival in patients with PFIC3 (progressive familial intrahepatic cholestasis type 3). Patients carrying at least one missense variation, with positive (decreased or normal) immuno-staining for canalicular MDR3, and a biliary phospholipid level over 6.9% of total biliary lipids were more likely to respond to ursodeoxycholic acid therapy and to exhibit prolonged native liver survival.

Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 ± 6.9 years of follow-up. Overall, 39.1% of participants had pre-diabetes mellitus, 14.0% had diabetes mellitus and 532 (11.8%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all p