Comprehensive characterization of protein modifications using mass spectrometry and dry blood spots.

PURPOSE: The main objective of this study is to characterize and analyze modified peptides in DBS samples. This includes deciphering their specific PTMs and understanding their potential impact on the population or disease cohort under study. EXPERIMENTAL DESIGN: Using mass spectrometry-based proteomic approaches, we performed a comprehensive analysis of DBS samples. Our focus was on the identification and quantification of modified peptides. We also took advantage of recent advances in DBS mass spectrometry to ensure accurate detection and quantification. RESULTS: A comprehensive analysis identified 972 modified peptides in DBS samples. Of these, a subset of 211 peptides was consistently present in all samples, highlighting their potential biological importance and relevance. This indicates a diverse spectrum of PTMs in the proteome of DBS samples. CONCLUSIONS AND CLINICAL RELEVANCE: Integration of mass spectrometry and proteomics has revealed a broad spectrum of modified peptides in DBS samples and highlighted their importance in biological processes and disease progression. Accurate detection of these PTMs may be critical for risk stratification and disease management. This study improves the understanding of molecular mechanisms underlying biological processes and disease development, providing important insights for clinical applications.

Acute and chronic effects of levosimendan in the ZSF1 obese rat model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by impaired cardiovascular reserve in which therapeutic options are scarce. Our aim was to evaluate the inodilator levosimendan in the ZSF1 obese rat model of HFpEF. Twenty-week-old male Wistar-Kyoto (WKY), ZSF1 lean (ZSF1 Ln) and ZSF1 obese rats chronically treated for 6-weeks with either levosimendan (1 mg/kg/day, ZSF1 Ob + Levo) or vehicle (ZSF1 Ob + Veh) underwent peak-effort testing, pressure-volume (PV) haemodynamic evaluation and echocardiography (n = 7 each). Samples were collected for histology and western blotting. In obese rats, skinned and intact left ventricular (LV) cardiomyocytes underwent in vitro functional evaluation. Seven additional ZSF1 obese rats underwent PV evaluation to assess acute levosimendan effects (10 µg/kg + 0.1 µg/kg/min). ZSF1 Ob + Veh presented all hallmarks of HFpEF, namely effort intolerance, elevated end-diastolic pressures and reduced diastolic compliance as well as increased LV mass and left atrial area, cardiomyocyte hypertrophy and increased interstitial fibrosis. Levosimendan decreased systemic arterial pressures, raised cardiac index, and enhanced LV relaxation and diastolic compliance in both acute and chronic experiments. ZSF1 Ob + Levo showed pronounced attenuation of hypertrophy and interstitial fibrosis alongside increased effort tolerance (endured workload raised 38 %) and maximum O2 consumption. Skinned cardiomyocytes from ZSF 1 Ob + Levo showed a downward shift in sarcomere length-passive tension relationship and intact cardiomyocytes showed decreased diastolic Ca2+ levels and enhanced Ca2+ sensitivity. On molecular grounds, levosimendan enhanced phosphorylation of phospholamban and mammalian target of rapamycin. The observed effects encourage future clinical trials with levosimendan in a broad population of HFpEF patients.

Desafios e perspectivas na atuação de estomaterapeutas durante a pandemia de COVID-19 / Challenges and perspectives in the work of stomatherapists during the COVID-19 pandemic

Objetivo: Analisar os desafios e perspectivas na atuação de estomaterapeutas durante a pandemia de COVID-19.Métodos: Pesquisa descritiva de abordagem qualitativa, por meio de entrevista semiestruturada com oito estomaterapeutas, selecionadas pela técnica snowball. Utilizou-se a Análise de Conteúdo, da qual emergiram três categorias: Desafios na atuação de estomaterapeutas durantea pandemia da COVID-19; Estratégias para viabilizar a assistência remota e presencial na estomaterapia; e Impacto da pandemia no cuidado de estomaterapia. Resultados: Os principais desafios citados foram: fechamento de ambulatórios e agravamento do quadro de saúde dos pacientes. As estratégias incluíram: adaptação da metodologia dos atendimentos, utilização de precauções-padrão e comunicação remota. Dentre as perspectivas futuras, destacam-se o crescimento da especialidade e valorização por outros profissionais da saúde. Conclusão: Houve diversos desafios na atuação de estomaterapeutas na pandemia, contornados, sobretudo, com a diversificação de estratégias assistenciais e modificações nos atendimentos. No entanto, destaca-se como perspectiva futura o aumento da visibilidade da especialidade. Descritores: Enfermagem; Estomaterapia; COVID-19

Objective: To analyze the challenges and perspectives in the work of stomatherapists during the COVID-19 pandemic. Methods: Descriptive research with a qualitative approach, through semi-structured interviews with eight stomatherapists, selected by the snowball technique. Content Analysis was used, emerging three categories: Challenges in the work of stomatherapists during the COVID-19 pandemic; Strategies to enable remote and face-to-face assistance in stomatherapy; and Impact of the pandemic on stomatherapy care. Results: The main challenges mentioned were: closure of outpatient clinics and worsening of the patients' health situation. The strategies included: adaptation of the care methodology, use of standard precautions and remote communication. Among the future perspectives, the growth of the specialty and appreciation by other health professionals stand out. Conclusion: There were several challenges in the work of stomatherapists in the pandemic, circumvented, above all, with the diversification of care strategies and modifications in care. However, the increased visibility of the specialty stands out as a future perspective. Descriptors:Nursing; Enterostomal Therapy; COVID-19.

Multiomics tools for improved atherosclerotic cardiovascular disease management.

Multiomics studies offer accurate preventive and therapeutic strategies for atherosclerotic cardiovascular disease (ASCVD) beyond traditional risk factors. By using artificial intelligence (AI) and machine learning (ML) approaches, it is possible to integrate multiple 'omics and clinical data sets into tools that can be utilized for the development of personalized diagnostic and therapeutic approaches. However, currently multiple challenges in data quality, integration, and privacy still need to be addressed. In this opinion, we emphasize that joined efforts, exemplified by the AtheroNET COST Action, have a pivotal role in overcoming the challenges to advance multiomics approaches in ASCVD research, with the aim to foster more precise and effective patient care.

Cardiovascular risk factors during pregnancy impact the postpartum cardiac and vascular reverse remodeling.

Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.

The PERInatal MYocardial Remodeling (PERIMYR) cohort study protocol: A prospective study of cardiac remodeling and "recovery" in pregnancy as a model to understand the impact of comorbidities in cardiac remodeling and reverse remodeling.

INTRODUCTION: Heart failure (HF) is among the leading causes of morbidity and mortality worldwide. Several conditions trigger left ventricular chronic pressure or volume overload, hypertrophy, systolic and diastolic dysfunction, leading to cardiac remodeling and a rapid progression toward HF. Therapeutic interventions elicit reverse remodeling (RR), a highly variable myocardial response that ranges from none to total ventricular structural/functional recovery. However, HF patients present several comorbidities and medications that mask a comprehensive molecular knowledge of RR and hinder the identification of potential biomarkers of its progression or prognosis. Therefore, instead of using this heterogeneous population or even animal models to understand myocardial remodeling, we propose studying pregnancy-induced cardiovascular remodeling and postpartum-induced RR. OBJECTIVES: To assess cardiovascular functional and structural adaptations during pregnancy and in postpartum, characterizing the associated molecular changes; as well as to explore the impact of hypertension, obesity and diabetes on these processes. METHODS: We will perform echocardiography and assess endothelial function and arterial stiffness (EndoPAT® and pulse wave velocity, respectively) and assess potential markers of remodeling and RR using plasma and urine samples from pregnant women. To translate to a HF context, we will determine the impact of risk factors (hypertension, obesity and diabetes) by studying subgroups of pregnant women with these comorbidities. RESULTS: Not applicable. CONCLUSION: We are convinced that understanding the impact of these comorbidities in such a homogeneous population, such as pregnant women, provides a valuable model to unveil the most relevant pathologic and often masked signaling pathways underlying cardiac remodeling and incomplete RR in a heterogeneous population, such as HF patients. Moreover, we expect to identify potential novel biomarkers of RR progression/prognosis more easily.

Coronary Artery Disease and Aortic Valve Stenosis: A Urine Proteomics Study.

Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AVS) are heart diseases accounting for most cardiac surgeries. These share many risk factors, such as age, diabetes, hypertension, or obesity, and similar pathogenesis, including endothelial disruption, lipid and immune cell infiltration, inflammation, fibrosis, and calcification. Unsuspected CAD and AVS are sometimes detected opportunistically through echocardiography, coronary angiography, and magnetic resonance. Routine biomarkers for early detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis. With a noninvasive collection, urine is appealing for biomarker assessment. We conducted a shotgun proteomics exploratory analysis of urine from 12 CAD and/or AVS patients and 11 controls to identify putative candidates to differentiate these diseases from healthy subjects. Among the top 20 most dysregulated proteins, TIMP1, MMP2 and vWF stood out, being at least 2.5× increased in patients with CAD/AVS and holding a central position in a network of protein-protein interactions. Moreover, their assessment in an independent cohort (19 CAD/AVS and 10 controls) evidenced strong correlations between urinary TIMP1 and vWF levels and a common cardiovascular risk factor - HDL (r = 0.59, p < 0.05, and r = 0.64, p < 0.01, respectively).

Optimization of a Protocol for Protein Extraction from Calcified Aortic Valves for Proteomics Applications: Development of a Standard Operating Procedure.

The comprehension of the pathophysiological mechanisms, the identification of druggable targets, and putative biomarkers for aortic valve stenosis can be pursued through holistic approaches such as proteomics. However, tissue homogenization and protein extraction are made difficult by tissue calcification. The reproducibility of proteome studies is key in clinical translation of the findings. Thus, we aimed to optimize a protocol for aortic valve homogenization and protein extraction and to develop a standard operating procedure (SOP), which researchers can use to maximize protein yield while reducing inter-laboratory variability. We have compared the protein yield between conventional tissue grinding in nitrogen followed by homogenization with a Potter apparatus with a more advanced bead-beating system. Once we confirmed the superiority of the latter, we further optimized it by testing the effect of beads size, the number of homogenization cycles, tube capacity, lysis buffer/tissue mass ratio, and two different lysis buffers. Optimal protein extraction was achieved with 2.8 mm zirconium dioxide beads, in two homogenization cycles, in the presence of 20 µL RIPA buffer/mg tissue, using 2 mL O-ring cryotubes. As a proof of concept of the usefulness of this SOP for proteomics, the AV proteome of men and women with aortic stenosis was characterized, resulting in the quantification of proteins across six orders of magnitude and uncovering some putative proteins dysregulated by sex.

Vascular Calcification and the Gut and Blood Microbiome in Chronic Kidney Disease Patients on Peritoneal Dialysis: A Pilot Study.

Vascular calcification (VC) is a frequent condition in chronic kidney disease (CKD) and a well-established risk factor for the development of cardiovascular disease (CVD). Gut dysbiosis may contribute to CVD and inflammation in CKD patients. Nonetheless, the role of gut and blood microbiomes in CKD-associated VC remains unknown. Therefore, this pilot study aimed to explore the link between gut and blood microbiomes and VC in CKD patients on peritoneal dialysis (CKD-PD). Our results showed relative changes in specific taxa between CKD-PD patients with and without VC, namely Coprobacter, Coprococcus 3, Lactobacillus, and Eubacterium eligens group in the gut, and Cutibacterium, Pajaroellobacter, Devosia, Hyphomicrobium, and Pelomonas in the blood. An association between VC and all-cause mortality risk in CKD-PD patients was also observed, and patients with higher mortality risk corroborate the changes of Eubacterium eligens in the gut and Devosia genus in the blood. Although we did not find differences in uremic toxins, intestinal translocation markers, and inflammatory parameters among CKD-PD patients with and without VC, soluble CD14 (sCD14), a nonspecific marker of monocyte activation, positively correlated with VC severity. Therefore, gut Eubacterium eligens group, blood Devosia, and circulating sCD14 should be further explored as biomarkers for VC, CVD, and mortality risk in CKD.

Application of Proteogenomics to Urine Analysis towards the Identification of Novel Biomarkers of Prostate Cancer: An Exploratory Study.

To identify new protein targets for PCa detection, first, a shotgun discovery experiment was performed to characterize the urinary proteome of PCa patients. This revealed 18 differentially abundant urinary proteins in PCa patients. Second, selected targets were clinically tested by immunoblot, and the soluble E-cadherin fragment was detected for the first time in the urine of PCa patients. Third, the proteogenome landscape of these PCa patients was characterized, revealing 1665 mutant protein isoforms. Statistical analysis revealed 6 differentially abundant mutant protein isoforms in PCa patients. Analysis of the likely effects of mutations on protein function and PPIs involving the dysregulated mutant protein isoforms suggests a protective role of mutations HSPG2*Q1062H and VASN*R161Q and an adverse role of AMBP*A286G and CD55*S162L in PCa patients. This work originally characterized the urinary proteome, focusing on the proteogenome profile of PCa patients, which is usually overlooked in the analysis of PCa and body fluids. Combined analysis of mass spectrometry data using two different software packages was performed for the first time in the context of PCa, which increased the robustness of the data analysis. The application of proteogenomics to urine proteomic analysis can be very enriching in mutation-related diseases such as cancer.

Pericardial Fluid Annexin A1 Is a Marker of Atrial Fibrillation in Aortic Stenosis: A Proteomics Analysis.

Atrial fibrillation (AF) is the most common arrhythmia with adverse clinical outcomes. Pericardial fluid (PF) mirrors the heart's pathophysiological status due to its proximity. This study aimed to characterise the PF proteome to identify new biomarkers of disease. Eighty-three patients submitted to aortic valve replacement surgery with severe aortic stenosis were selected, and their baseline echocardiographic and clinical variables were documented. Thirteen samples were selected blindly for proteome characterisation following a shotgun (GeLC-MS/MS) and a label-free quantification approach (LFQ). According to previous AF history, a partial least squares discriminant analysis (PLS-DA) was conducted, and the top 15 variables important in projection were identified. To inquire potential biomarkers, ROC curves were designed using LFQ data. Target proteins were further validated by ELISA, in both pericardial fluid and serum. Proteome analysis uncovered nine proteins up- and downregulated ≥2-fold. Annexin A1, annexin A2, and vimentin were among the top 15 most important variables for group discrimination in PLS-DA. Protein-protein interaction and gene ontology enrichment analysis presented functional interaction among identified proteins, which were all part of focal adhesion sites. Annexin A1 was increased in the pericardial fluid of AF patients but not in serum when quantified by ELISA. Annexin A1 is a novel pericardial fluid biomarker of AF in patients with severe aortic stenosis.

Sexual dimorphism in cardiac remodeling: the molecular mechanisms ruled by sex hormones in the heart.

Heart failure (HF) is growing in prevalence, due to an increase in aging and comorbidities. Heart failure with reduced ejection fraction (HFrEF) is more common in men, whereas heart failure with preserved ejection fraction (HFpEF) has a higher prevalence in women. However, the reasons for these epidemiological trends are not clear yet. Since HFpEF affects mostly postmenopausal women, sex hormones should play a pivotal role in HFpEF development. Furthermore, for HFpEF, contrary to HFrEF, effective therapeutic approaches are missing. Interestingly, studies evidenced that some therapies can have better results in women than in HFpEF men, emphasizing the necessity of understanding these observations at a molecular level. Thus, herein, we review the molecular mechanisms of estrogen and androgen actions in the heart in physiological conditions and explain how its dysregulation can lead to disease development. This clarification is essential in the road for an effective personalized management of HF, particularly HFpEF, towards the development of sex-specific therapeutic approaches.

Mining the Biomarker Potential of the Urine Peptidome: From Amino Acids Properties to Proteases.

Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine.

The potential impact of salivary peptides in periodontitis.

Periodontitis is a complex immune-inflammatory condition characterized by the disruption of the periodontal ligament and subsequent formation of periodontal pockets, and by alveolar bone loss, often resulting in tooth loss. A myriad of factors, namely, genetic, metabolic, immunological, and inflammatory, is associated with progression of periodontitis. Periodontitis is also associated with systemic conditions such as neoplastic disorders, obesity, and diabetes. The current diagnosis of this disease relies on clinical measurements such as clinical attachment loss and probing depth, which have poor precision due to patient, operator and probe-related factors. Thus, there is a need to develop reliable, objective, and reproducible biomarkers for early diagnosis of periodontitis. In this regard, saliva, with contributions from the gingival crevicular fluid, holds great potential. However, most of the information on biomarkers of periodontium-related salivary proteins has come from studies on the molecular pathogenesis of periodontitis. In periodontitis, a more holistic approach, such as the use of -omics technologies, for biomarker discovery, is needed. Herein, we review the biomarkers proposed to date for the assessment of periodontitis, with emphasis on the role of salivary peptides in periodontitis and their assessment by high-throughput saliva proteomics. We also discuss the challenges pertaining to the identification of new periodontitis biomarkers in saliva.

Automatic text-mining as an unbiased approach to uncover molecular associations between periodontitis and coronary artery disease.

The increasing prevalence of periodontal and cardiovascular diseases is the result of a sedentary lifestyle associated with poor diet, obesity, hypercholesterolaemia, smoking habits, alcohol consumption and stress. The present study aims to uncover molecular associations between periodontitis and coronary heart disease using an unbiased strategy of automatic text mining traditionally applied to bibliometric studies. A total of 1590 articles on these diseases were retrieved from the Web of knowledge database and searched using the VOS viewer to create a network of keywords associated with both diseases. These data were supplemented with data from DisGeNET, which stores known associations to either periodontitis or coronary heart disease. Overall, the automated text mining approach presented here highlighted inflammatory molecules as common associations between periodontitis and coronary heart disease. Specifically, this study showed that molecules such as C-reactive protein, interleukins 6 and 1-ß, myeloperoxidase, and matrix metalloproteinase 9 are simultaneously associated with periodontitis and coronary artery disease by both text mining and DisGeNET analyses. This association validates the multiplex assessment of salivary inflammatory markers as a tool to assess cardiovascular disease risk and could become an important tool to identify common molecular targets to monitor both diseases simultaneously. In addition, the text mining protocol and subsequent data processing and methods using bioinformatics tools could be useful to uncover links between other diseases.

Consumo de bebidas alcoólicas e prática do binge drinking entre cabeleireiros / Consumption of alcoholic beverages and practice of binge drinking among hairdressers

RESUMO Objetivo verificar o consumo de bebidas alcóolicas e a prática do binge drinking entre os cabeleireiros. Métodos estudo transversal realizado com 51 profissionais de salões de beleza. Utilizou-se de um questionário com características sociodemográficas e sobre as práticas do consumo de bebidas alcoólicas. Para a identificação do uso em binge drinking, pautou-se a questão-chave. Realizou-se a análise estatística descritiva e inferencial. Resultados 84,3% eram consumidores de álcool, 51,0% tinham de um a dez anos de consumo e 72,5% consumiam a cerveja. Em relação ao uso em binge, 37,3% da amostra faziam uso ocasional de risco, pelo menos, uma vez ao mês. Os maiores índices de binge drinking estavam relacionados ao gênero masculino, aos solteiros e jovens e a religião evangélica foi associada a um menor ou nenhum consumo de bebidas alcoólicas. Conclusão os dados apontaram o consumo alcoólico e o uso em binge frequente relacionados à provável dependência alcoólica.

ABSTRACT Objective to verify the consumption of alcoholic beverages and the practice of binge drinking among hairdressers. Methods cross-sectional study conducted with 51 beauty salon professionals. We used a questionnaire with socio-demographic characteristics and about the practices of consumption of alcoholic beverages. For the identification of the use in binge drinking, the key question was guided. Descriptive and inferential statistical analysis was performed. Results 84.3% were alcohol consumers, 51.0% had between one and ten years of consumption and 72.5% consumed beer. In relation to the use in binging, 37.3% of the sample made occasional use of risk, at least once a month. The highest rates of binge drinking were related to male gender, single and young and the evangelical religion was associated with a lower or no consumption of alcoholic beverages. Conclusion the data pointed to alcohol consumption and frequent binge use related to likely alcohol dependence.

Effect of the acromial inferolateral tilt on subacromial impingement syndrome: a retrospective magnetic resonance imaging assessment.

OBJECTIVE: To evaluate the effect of acromial inferolateral tilt on subacromial impingement syndrome. MATERIALS AND METHODS: The acromial inferolateral tilt was retrospectively quantified by two researchers on 346 shoulder magnetic resonance images using the glenoacromial (between the inferior proximal acromial surface and the glenoidal face) and acromioclavicular (between the axis of the proximal acromion and distal clavicle) angles. RESULTS: The glenoacromial angle was associated with subacromial impingement syndrome (p < 0.001) and complete supraspinatus tendon rupture (p < 0.001), and the acromioclavicular angle was associated with partial or complete supraspinatus tendon rupture (p = 0.003). The area under the receiver operating characteristic curve (AUC), best cut-off angle, and odds ratio (OR) of the glenoacromial angle for impingement syndrome were 0.579 (95% confidence interval [CI]: 0.508-0.649; p = 0.032), 72°, and 2.1 (95% CI: 1.136-4.053), respectively. For complete supraspinatus tendon rupture, the AUC, best cut-off angle, and OR of the glenoacromial angle were 0.731 (95% CI: 0.626-0.837; p = 0.001), 69°, and 8.496 (95% CI: 2.883-28.33), respectively. For partial or complete supraspinatus tendon rupture, the AUC, best cut-off angle and OR of the acromioclavicular angle were 0.617 (95% CI: 0.539-0.694; p = 0.002), 17°, and 3.288 (95% CI: 1.886-5.768), respectively. Interobserver agreement found for the glenoacromial and acromioclavicular angles were 0.737 (95% CI: 0.676-0.787; p < 0.001) and 0.507 (95% CI: 0.391-0.601; p = 0.001), respectively. CONCLUSION: Inferolateral acromial tilt may have some impact on subacromial impingement syndrome; however, the best quantification method identified (glenoacromial angle) showed a moderate interobserver agreement and a fair performance to assess the risk of complete supraspinatus tendon rupture.

OBJETIVO: Avaliar a contribuição da inclinação inferolateral do acrômio na síndrome do impacto subacromial. MATERIAIS E MÉTODOS: A inclinação inferolateral do acrômio foi quantificada retrospectivamente por dois pesquisadores em 346 ressonâncias magnéticas de ombro por meio dos ângulos glenoacromial (entre a superfície inferior proximal do acrômio e a face glenoidal no plano coronal) e acromioclavicular (entre o eixo do acrômio proximal e o eixo da clavícula distal no plano coronal). RESULTADOS: Houve associação entre ângulo glenoacromial e síndrome do impacto subacromial (p < 0,001) e ruptura completa do tendão supraespinal (p < 0,001). Ângulo acromioclavicular associou-se a ruptura parcial ou completa do tendão supraespinal (p = 0,003). A área sob a curva (area under the curve - AUC) característica de operação do receptor, o melhor ângulo de corte e a razão de chances (odds ratio - OR) do ângulo glenoacromial para a síndrome do impacto foram, respectivamente: 0,579 (intervalo de confiança [IC] 95%: 0,508-0,649; p = 0,032), 72° e 2,1 (IC 95%: 1,136-4,053). Para ruptura completa do tendão supraespinal, a AUC, o melhor ângulo de corte e a OR do ângulo glenoacromial foram, respectivamente: 0,731 (IC 95%: 0,626-0,837; p = 0.001), 69° e 8,496 (IC 95%: 2,883-28,33). Para ruptura parcial ou completa do tendão supraespinal, a AUC, o melhor ângulo de corte e a OR do ângulo acromioclavicular foram, respectivamente: 0,617 (IC 95%: 0,539-0,694; p = 0,002), 17° e 3,288 (IC 95%: 1,886-5,768). As concordâncias interobservador encontradas para os ângulos glenoacromial e acromioclavicular foram, respectivamente: 0,737 (IC 95%: 0,676-0,787; p < 0,001) e 0,507 (IC 95%: 0,391-0,601; p = 0,001). CONCLUSÃO: Inclinação inferolateral do acrômio pode determinar alguma influência sobre a síndrome do impacto subacromial, entretanto, o melhor método de quantificação identificado (o ângulo glenoacromial) apresentou moderada concordância interobservador e desempenho moderado para estratificar o risco de ruptura completa do tendão supraespinal.

Effect of the acromial inferolateral tilt on subacromial impingement syndrome: a retrospective magnetic resonance imaging assessment / A contribuição da inclinação inferolateral do acrômio na síndrome do impacto subacromial: uma avaliação retrospectiva por ressonância magnética

Abstract Objective: To evaluate the effect of acromial inferolateral tilt on subacromial impingement syndrome. Materials and Methods: The acromial inferolateral tilt was retrospectively quantified by two researchers on 346 shoulder magnetic resonance images using the glenoacromial (between the inferior proximal acromial surface and the glenoidal face) and acromioclavicular (between the axis of the proximal acromion and distal clavicle) angles. Results: The glenoacromial angle was associated with subacromial impingement syndrome (p < 0.001) and complete supraspinatus tendon rupture (p < 0.001), and the acromioclavicular angle was associated with partial or complete supraspinatus tendon rupture (p = 0.003). The area under the receiver operating characteristic curve (AUC), best cut-off angle, and odds ratio (OR) of the glenoacromial angle for impingement syndrome were 0.579 (95% confidence interval [CI]: 0.508-0.649; p = 0.032), 72°, and 2.1 (95% CI: 1.136-4.053), respectively. For complete supraspinatus tendon rupture, the AUC, best cut-off angle, and OR of the glenoacromial angle were 0.731 (95% CI: 0.626-0.837; p = 0.001), 69°, and 8.496 (95% CI: 2.883-28.33), respectively. For partial or complete supraspinatus tendon rupture, the AUC, best cut-off angle and OR of the acromioclavicular angle were 0.617 (95% CI: 0.539-0.694; p = 0.002), 17°, and 3.288 (95% CI: 1.886-5.768), respectively. Interobserver agreement found for the glenoacromial and acromioclavicular angles were 0.737 (95% CI: 0.676-0.787; p < 0.001) and 0.507 (95% CI: 0.391-0.601; p = 0.001), respectively. Conclusion: Inferolateral acromial tilt may have some impact on subacromial impingement syndrome; however, the best quantification method identified (glenoacromial angle) showed a moderate interobserver agreement and a fair performance to assess the risk of complete supraspinatus tendon rupture.

Resumo Objetivo: Avaliar a contribuição da inclinação inferolateral do acrômio na síndrome do impacto subacromial. Materiais e Métodos: A inclinação inferolateral do acrômio foi quantificada retrospectivamente por dois pesquisadores em 346 ressonâncias magnéticas de ombro por meio dos ângulos glenoacromial (entre a superfície inferior proximal do acrômio e a face glenoidal no plano coronal) e acromioclavicular (entre o eixo do acrômio proximal e o eixo da clavícula distal no plano coronal). Resultados: Houve associação entre ângulo glenoacromial e síndrome do impacto subacromial (p < 0,001) e ruptura completa do tendão supraespinal (p < 0,001). Ângulo acromioclavicular associou-se a ruptura parcial ou completa do tendão supraespinal (p = 0,003). A área sob a curva (area under the curve - AUC) característica de operação do receptor, o melhor ângulo de corte e a razão de chances (odds ratio - OR) do ângulo glenoacromial para a síndrome do impacto foram, respectivamente: 0,579 (intervalo de confiança [IC] 95%: 0,508-0,649; p = 0,032), 72° e 2,1 (IC 95%: 1,136-4,053). Para ruptura completa do tendão supraespinal, a AUC, o melhor ângulo de corte e a OR do ângulo glenoacromial foram, respectivamente: 0,731 (IC 95%: 0,626-0,837; p = 0.001), 69° e 8,496 (IC 95%: 2,883-28,33). Para ruptura parcial ou completa do tendão supraespinal, a AUC, o melhor ângulo de corte e a OR do ângulo acromioclavicular foram, respectivamente: 0,617 (IC 95%: 0,539-0,694; p = 0,002), 17° e 3,288 (IC 95%: 1,886-5,768). As concordâncias interobservador encontradas para os ângulos glenoacromial e acromioclavicular foram, respectivamente: 0,737 (IC 95%: 0,676-0,787; p < 0,001) e 0,507 (IC 95%: 0,391-0,601; p = 0,001). Conclusão: Inclinação inferolateral do acrômio pode determinar alguma influência sobre a síndrome do impacto subacromial, entretanto, o melhor método de quantificação identificado (o ângulo glenoacromial) apresentou moderada concordância interobservador e desempenho moderado para estratificar o risco de ruptura completa do tendão supraespinal.

De novo sequencing of proteins by mass spectrometry.

INTRODUCTION: Proteins are crucial for every cellular activity and unraveling their sequence and structure is a crucial step to fully understand their biology. Early methods of protein sequencing were mainly based on the use of enzymatic or chemical degradation of peptide chains. With the completion of the human genome project and with the expansion of the information available for each protein, various databases containing this sequence information were formed. AREAS COVERED: De novo protein sequencing, shotgun proteomics and other mass-spectrometric techniques, along with the various software are currently available for proteogenomic analysis. Emphasis is placed on the methods for de novo sequencing, together with potential and shortcomings using databases for interpretation of protein sequence data. EXPERT OPINION: As mass-spectrometry sequencing performance is improving with better software and hardware optimizations, combined with user-friendly interfaces, de-novo protein sequencing becomes imperative in shotgun proteomic studies. Issues regarding unknown or mutated peptide sequences, as well as, unexpected post-translational modifications (PTMs) and their identification through false discovery rate searches using the target/decoy strategy need to be addressed. Ideally, it should become integrated in standard proteomic workflows as an add-on to conventional database search engines, which then would be able to provide improved identification.