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To describe the performance of machine learning (ML) applied to predict future metabolic syndrome (MS), and to estimate lifestyle changes effects in MS predictions.We analyzed data from 17,182 adults attending a checkup program sequentially (37,999 visit pairs) over 17 years. Variables on sociodemographic attributes, clinical, laboratory, and lifestyle characteristics were used to develop ML models to predict MS [logistic regression, linear discriminant analysis, k-nearest neighbors, decision trees, Light Gradient Boosting Machine (LGBM), Extreme Gradient Boosting]. We have tested the effects of changes in lifestyle in MS prediction at individual levels.All models showed adequate calibration and good discrimination, but the LGBM showed better performance (Sensitivity = 87.8 %, Specificity = 70.2 %, AUC-ROC = 0.86). Causal inference analysis showed that increasing physical activity level and reducing BMI by at least 2 % had an effect of reducing the predicted probability of MS by 3.8 % (95 % CI = -4.8 %; -2.7 %).ML models based on data from a checkup program showed good performance to predict MS and allowed testing for effects of lifestyle changes in this prediction. External validation is recommended to verify models' ability to identify at-risk individuals, and potentially increase their engagement in preventive measures.

Epidemiological studies demonstrate the role of early and intensive glycemic control in the prevention of micro and macrovascular disease in both type 1 and type 2 diabetes mellitus (DM). Hyperglycemia elicits several pathways related to the etiopathogenesis of cardiovascular disease (CVD), including the generation of advanced glycation end products (AGEs). In this review, we revisit the role played by AGEs in CVD based in clinical trials and experimental evidence. Mechanistic aspects concerning the recognition of AGEs by the advanced glycosylation end product-specific receptor (AGER) and its counterpart, the dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST) and soluble AGER are discussed. A special focus is offered to the AGE-elicited pathways that promote cholesterol accumulation in the arterial wall by enhanced oxidative stress, inflammation, endoplasmic reticulum stress and impairment in the reverse cholesterol transport (RCT).

Produtos de glicação avançada (AGEs) associam-se, independentemente, com o risco cardiovascular, e constituem uma das bases da memória metabólica, a qual fundamenta a manutenção do risco elevado de complicações do diabetes mellitus (DM) previamente descompensado, mesmo após a normalização da glicemia. Avaliou-se o efeito da redução da modificação da albumina por AGEs sobre o efluxo de colesterol, conteúdo intracelular de lípides, expressão de genes envolvidos no fluxo de lípides, taxa de decaimento e conteúdo do receptor ABCA-1 em macrófagos. Além disso, foi investigado o tempo de persistência do efeito da albumina modificada por AGEs na sensibilização de macrófagos à resposta inflamatória e no prejuízo da remoção de colesterol celular. Albumina foi isolada do soro de indivíduos com DM1 e DM2 antes e após melhora do controle glicêmico (pré- e pós-CG), por cromatografia rápida para separação de proteínas e extração alcoólica. Albumina bovina modificada in vitro por AGEs foi preparada pela incubação com glicolaldeído (albumina-GAD) e albumina controle, com tampão fosfato. Macrófagos derivados de células indiferenciadas da medula óssea de camundongos enriquecidos em 14C- colesterol foram incubados com albumina pré-CG e pós-CG e o efluxo de colesterol determinado após incubação com apoA-I ou HDL2. Coloração com Oil Red O foi utilizada para quantificação do conteúdo intracelular de lípides. A expressão gênica foi determinada em macrófagos J774 por RT-qPCR e a taxa de degração de ABCA-1, mediante tratamento destas células com ciclohexamida. O efluxo de colesterol (%; n = 3) foi maior nas células incubadas com albumina pós-CG (5,5 ± 0,6 e 11,1 ± 1,2; respectivamente para apo-AI e HDL2) em comparação com a albumina pré-CG (2,80 ± 0,7 e 4,4 ± 0,8; p < 0,05). O conteúdo de lípides (?m2 ) foi menor nas células tratadas com albumina pós-CG incubadas com apo-AI (0,6 ± 0,3) e HDL2 (1,2 ± 0,4) em comparação com a albumina pré-CG (2,8 ± 0,4 e 2,6 ± 0,03, respectivamente). A expressão de Abca1 foi semelhante entre os grupos, mas a de Nox4 e Jak2 foi, respectivamente, reduzida e aumentada pela albumina pós-CG em comparação com a albumina pré-CG. O conteúdo proteico de ABCA-1 foi 94% menor em macrófagos tratados com albumina pré-CG em comparação a pós-CG. Albumina isolada de indivíduos DM1 com controle glicêmico inadequado em comparação àquela de indivíduos controles, induziu maior taxa de decaimento (20%) do ABCA-1 em macrófagos. A albumina-GAD e a albumina isolada de DM pré-CG favoreceram maior secreção de TNF e IL-6 por macrófagos estimulados com lipopolissacarídeo e este efeito persistiu mesmo após 8 h da remoção do estímulo pela albumina modificada por AGEs. O mesmo foi observado para a redução do efluxo de colesterol, a qual persistiu após 9 h da retirada do insulto pela albumina modificada por AGEs. Em conclusão, a melhora do CG refletida pela redução da modificação de albumina por AGEs melhorou a expressão de genes que modulam a funcionalidade do ABCA-1, reduziu a taxa de degradação deste receptor e aumentou seu conteúdo em macrófagos, o que se vinculou à melhora do efluxo de colesterol e redução do acúmulo intracelular de lípides. Os efeitos da albumina modificada por AGEs são persistentes em macrófagos e condizem com alterações na homeostase de lípídes e estresse inflamatórios baseados em modelo de memória metabólica celular. Advanced glycation products (AGEs) are independently associated with cardiovascular risk and constitute one of the bases of metabolic memory, which supports the maintenance of high-risk complications in previously decompensated diabetes mellitus (DM), even after normalization of glycemia. It was evaluated the effect of the reduction in albumin modification by AGEs on the cholesterol efflux, intracellular lipid content, expression of genes involved in lipid flux, ABCA-1 content, and decay rate in macrophages. In addition, it was investigated the persistence time of AGE-albumin effect on macrophage sensitization to inflammation and damage in cholesterol efflux. Serum albumin was isolated from subjects with T1DM and T2DM before and after improvement of the glycemic control (GC) by fast protein liquid chromatography and alcoholic extraction. Bovine albumin was in vitro modified by AGEs by incubation with glycolaldehyde (GAD-albumin) and control albumin with phosphate buffer. Bone marrow-derived macrophages enriched with 14C-cholesterol were incubated with albumin isolated bGC and aGC and cholesterol efflux determined after incubation with apoA-I or HDL2. Staining with Oil Red O was used for the quantification of intracellular lipid content. Cholesterol efflux to apo-AI and HDL2 (%; n = 3) was higher in cells incubated with albumin isolated aGC (5.5 ± 0.6 and 11.1 ± 1.2, respectively) as compared to albumin isolated bGC (2.80 and 4.4 ± 0.8, respectively; p < 0.05). Lipid content (?m2 ) was lower in cells treated with albumin isolated aGC and incubated with apoA-I (0.6 ± 0.3) and HDL2 (1.2 ± 0.4) compared to albumin isolated bGC (2.8 ± 0.4 and 2.6 ± 0.03, respectively). The expression of Abca1 was similar between groups, but Nox4 and Jak2 were respectively reduced and increased by post-GC albumin compared to albumin in the bGC period. ABCA-1 protein levels were 94% lower in macrophages treated with albumin from bGC period as compared to albumin from aGC. Albumin from poorly controlled T1DM subjects induced a 20% increase in the ABCA-1 decay rate. As compared to non-modified control albumin and albumin isolated from control subjects, GAD-albumin and albumin isolated from subjects with DM bGC induced a higher secretion of tumor necrosis factor (TNF) and interleukin-6 (IL-6) by macrophages stimulated with lipopolysaccharides and this effect persisted even after 8 h of the removal of AGE-albumin from cells. The same was observed for the reduction in cholesterol efflux that persisted 9 h after the removal of AGE- albumin. In conclusion, the improvement in GC reflected by the reduction of albumin modification by AGEs, favored the expression. of genes that positively modulate ABCA-1 functionality, reduced ABCA-1 intracellular degradation, and increased the ABCA-1 protein level that was related to the improvement of cholesterol efflux and reduced intracellular lipid accumulation. The effects of AGE-albumin are persistent in macrophages favoring alteration in cellular lipid homeostasis and inflammatory stress according to a metabolic memory cell-based model.

Background and aims Abnormalities in lipid metabolism, accumulation of uremic toxins and advanced glycation end products may contribute to worsening atherosclerosis. This study characterized the glycation and carbamoylation profile of serum albumin isolated from individuals with diabetic kidney disease and its influence on cholesterol efflux. Material and methods 49 patients with type 2 diabetes (T2DM) and different eGFR evaluated glycation and carbamoylation profile by measurement of carboxymethyl lysine (CML) and carbamoylated proteins (CBL) in plasma by ELISA, homocitrulline (HCit) in plasma by colorimetry. In the isolated albumins, we quantified CBL (ELISA) and total AGE and pentosidine by fluorescence. Macrophages were treated with albumin isolated, and 14C-Cholesterol efflux mediated by HDL2 or HDL3 was measured. Kruskal-Wallis test, Jonckheere-Terpstra test and Brunner's posttest were used for comparisons among groups. Results Determination of CML, HCit, CBL in plasma, as total AGE and pentosidine in albumins, did not differ between groups; however, CBL in the isolated albumins was higher in the more advanced stages of CKD (p = 0.0414). There was reduction in the 14C-cholesterol efflux after treatment for 18 h with albumin isolated from patients with eGFR Conclusions Albumins isolated from individuals with T2DM and eGFR

Background and aimsDiabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER).MethodsIndividuals with DKD were divided into eGFR> 60 mL/min/1.73 m2plus AER stages A1 and A2 (n = 10) and eGFRn = 25) and matched by age with control subjects (eGFR> 60;n = 8).ResultsTargeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR14C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFRConclusionThe increase in apoD and apoA-IV could contribute to counteracting the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD.

Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements worsening kidney function and enhancing cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications bringing up the participation of untraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in HDL proteome and functionality. We analyzed HDL composition, proteome, chemical modification and functionality in non-dialytic DKD subjects categorized according to estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: DKD individuals were divided in eGFR>60 mL/min/1.73 m2 plus AER stages A1 and A2 (n=10) and eGFR60; n=8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more expressed in eGFRapoD) and apoA-IV. HDL from eGFR14C-cholesterol from macrophages (33%) in comparison to controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups but HDL from eGFRConclusion: The increment in ApoD and ApoA-IV seems to counteract the HDL chemical modification by AGE and carbamoylation that contributes for HDL loss of function in well-established DKD.

Advanced glycated albumin (AGE-albumin) impairs cholesterol efflux and contributes to inflammation in macrophages. The current study evaluated: (1) the persistence of the deleterious effect of AGE-albumin in cholesterol efflux and in inflammation, and (2) how metabolic control in diabetes mellitus (DM) contributes to attenuate the deleterious role of AGE-albumin in macrophage cholesterol homeostasis. Methods: AGE-albumin was produced in vitro or isolated from uncontrolled DM subjects’ serum before (bGC) and after improved glycemic control (aGC). Albumin samples were incubated with bone marrow-derived macrophages and 14C-cholesterol efflux or LPS- induced cytokine secretion were determined immediately, or after cell resting in culture media alone. The ABCA-1 degradation rate was determined after cell incubation with cycloheximide, and ABCA1 protein level by immunoblot. Oil Red O staining was used to assess intracellular lipid accumulation. Results: A persistent effect of AGE-albumin was observed in macrophages in terms of the secretion of inflammatory cytokines and reduced cholesterol efflux. HDL-mediated 14C-cholesterol efflux was at least two times higher in macrophages treated with aCG-albumin as compared to bGC-albumin, and intracellular lipid content was significantly reduced in aGC-albumin-treated cells. As compared to bGC-albumin, the ABCA-1 protein content in whole cell bulk was 94% higher in aCG-albumin. A 20% increased ABCA-1 decay rate was observed in macrophages treated with albumin from poorly controlled DM. AGE-albumin has a persistent deleterious effect on macrophage lipid homeostasis and inflammation. The reduction of AGEs in albumin ameliorates cholesterol efflux.

Maintenance of high-quality cardiopulmonary resuscitation (CPR) in refractory ventricular fibrillation (VF) and attempted treatment of the underline cause is associated with increased survival in prolonged cardiac arrest (CA). Thrombolysis targeting treatment of presumable acute myocardial infarction during CA, although plausible, is not routinely recommended. However, with the increase in technology to aid diagnosis during cardiac arrest, it is possible to more accurately infer patients who can benefit. This paper is a case report of a patient who presented an out-hospital subtle CA attended promptly by an alone rescuer. Due to geographical and communication conditions, the rescue system was not activated and the patient was transferred to the closer emergency department after 30 minutes of collapse by the rescuer's own means. The patient was resuscitated by a complete team in a satellite emergency unit and monitored with hand-free paddles. The rhythm was recurrent VF and there was rigorous CPR. The electrocardiogram filter showed ST-segment elevation in a short moment of sustained sinus rhythm. Intra-arrest thrombolytic therapy was performed after 25 minutes of in-hospital CA and immediate return to spontaneous circulation (ROSC) observed. Patient underwent cardiac catheterization with angioplasty of the anterior descending coronary and complete neurological recovery. This case report aims to demonstrate the possible effectiveness of thrombolysis during prolonged CA when ST-segment elevation myocardial infarction diagnosis is made by electrocardiogram filter. High-quality CPR and individualization with underlining cause treatment can promote ROSC, neurological recovery and discharge with good quality of life.

Munchhausen’s syndrome (MS) is a chronic factitious disorder characterized by the intentional production of clinical symptoms without external incentive. One type of MS is factitious Cushing syndrome, an extremely rare clinical situation in which the diagnosis is challenging mainly due to interference of the exogenous medication in cortisol immunoassays. We described a 26-year-old woman who was originally diagnosed with a macroprolactinoma and during follow-up developed clinical and laboratorial hypercortisolism. A transsphenoidal surgery was performed and immunohistochemistry revealed positive and diffuse staining for both hormones. Four years later, her hypercortisolism recurred and the confirmation of factitious Cushing syndrome was delayed due to conflicting laboratorial results. There are few cases in the literature of factitious Cushing syndrome, and only one had a fatal outcome. The diagnosis of this condition is complex and includes cyclic Cushing syndrome in the differential diagnosis. These patients have high morbidity and increased mortality risk and are likely to have other psychiatric disorders. Prednisone was identified as the culprit in the majority of the cases.

References 1. Minanni CA, De Almeida Cardoso AL, de Albuquerque Albuquerque EV, Pinto Brito L, Lima Lopes LM, Glezer A, Del Rosario Ugarte Verduguez E, Bilharinho De Mendonca B, Bronstein MD, Machado MC, Fragoso MCBV. Fatal factitious Cushing syndrome (Munchhausen’s syndrome) in a patient with macroprolactinoma and silent corticotrophinoma: case report and literature review. Clin Diabetes Endocrinol. 2015;1:3. 2. Minanni CA, Cardoso ALA, Albuquerque EVA, Lopes LML, Glezer A, Verduguez ERU, Gallucci-neto J, Gattaz WF, Mendonca BB, Bronstein MD, Machado MC, Fragoso MCBV. Fatal factitious Cushing’s syndrome (Munchhausen’s syndrome) in a patient with a prolactinoma and silent corticotrophinoma: case report and literature review. J Women’s Health Care. 2014;3:162. • We accept pre-submission inquiries • Our selector tool helps you to find the most relevant journal • We provide round the clock customer support • Convenient online submission • Thorough peer review • Inclusion in PubMed and all major indexing services • Maximum visibility for your research