Cutoffs for white-coat and masked blood pressure effects: an ambulatory blood pressure monitoring study.

The values used to define white-coat and masked blood pressure (BP) effects are usually arbitrary. This study aimed at investigating the accuracy of various cutoffs based on the differences (ΔBP) between office BP (OBP) and 24h-ambulatory BP monitoring (ABPM) to identify white-coat (WCH) and masked (MH) hypertension, which are phenotypes coupled with adverse prognosis. This cross-sectional study included 11,350 [Derivation cohort; 45% men, mean age = 55.1 ± 14.1 years, OBP = 132.1 ± 17.6/83.9 ± 12.5 mmHg, 24 h-ABPM = 121.6 ± 11.4/76.1 ± 9.6 mmHg, 25% using antihypertensive medications (AH)] and 7220 (Validation cohort; 46% men, mean age = 58.6 ± 15.1 years, OBP = 136.8 ± 18.7/87.6 ± 13.0 mmHg, 24 h-ABPM = 125.5 ± 12.6/77.7 ± 10.3 mmHg; 32% using AH) unique individuals who underwent 24 h-ABPM. We compared the sensitivity, specificity, positive and negative predictive values and area under the curve (AUC) of diverse ΔBP cutoffs to detect WCH (ΔsystolicBP/ΔdiastolicBP = 28/17, 20/15, 20/10, 16/11, 15/9, 14/9 mmHg and ΔsystolicBP = 13 and 10 mmHg) and MH (ΔsystolicBP/ΔdiastolicBP = -14/-9, -5/-2, -3/-1, -1/-1, 0/0, 2/2 mmHg and ΔsystolicBP = -5 and -3mmHg). The 20/15 mmHg cutoff showed the best AUC (0.804, 95%CI = 0.794-0.814) to detect WCH, while the 2/2 mmHg cutoff showed the highest AUC (0.741, 95%CI = 0.728-0.754) to detect MH in the Derivation cohort. Both cutoffs also had the best accuracy to detect WCH (0.767, 95%CI = 0.754-0.780) and MH (0.767, 95%CI = 0.750-0.784) in the Validation cohort. In secondary analyses, these cutoffs had the best accuracy to detect individuals with higher and lower office-than-ABPM grades in both cohorts. In conclusion, the 20/15 and 2/2 mmHg ΔBP cutoffs had the best accuracy to detect hypertensive patients with WCH and MH, respectively, and can serve as indicators of marked white-coat and masked BP effects derived from 24 h-ABPM.

The influence of sex on left ventricular remodeling in patients with aortic dissection.

AIMS: Patients with aortic dissection have a high prevalence of left ventricular structural alterations, including left ventricular hypertrophy (LVH), but little is known about the impact of sex on this regard. This study compared clinical, cardiac, and prognostic characteristics between men and women with aortic dissection. METHODS: We retrospectively assessed clinical and echocardiographic characteristics, and 1-year mortality in 367 aortic dissection patients (30% women; 66% with Stanford-A) who underwent echocardiography 60 days before or after the diagnosis of aortic dissection from three Brazilian centers. RESULTS: Men and women had similar clinical characteristics, except for higher age (59.4 ±â€Š13.4 vs. 55.9 ±â€Š11.6 years; P = 0.013) and use of antihypertensive classes (1.4 ±â€Š1.3 vs. 1.1 ±â€Š1.2; P = 0.024) and diuretics (32 vs. 19%; P = 0.004) in women compared with men. Women had a higher prevalence of LVH (78 vs. 65%; P = 0.010) and lower prevalence of normal left ventricular geometry (20 vs. 10%; P = 0.015) than men. Logistic regression analysis adjusted for confounding factors showed that women were less likely to have normal left ventricular geometry (odds ratio, 95% confidence interval = 0.42, 0.20-0.87; P = 0.019) and were more likely to have LVH (odds ratio, 95% confidence interval = 1.91, 1.11-3.27; P = 0.019). Conversely, multivariable Cox-regression analysis showed that women had a similar risk of death compared to men 1 year after aortic dissection diagnosis (hazard ratio, 95% confidence interval = 1.16, 0.77-1.75; P = 0.49). CONCLUSION: In aortic dissection patients, women were typically older, had higher use of antihypertensive medications, and exhibited a greater prevalence of LVH compared with men. However, 1-year mortality after aortic dissection diagnosis did not differ between men and women.

Photoproduction of K

K^{+}K^{-} pairs may be produced in photonuclear collisions, either from the decays of photoproduced ϕ(1020) mesons or directly as nonresonant K^{+}K^{-} pairs. Measurements of K^{+}K^{-} photoproduction probe the couplings between the ϕ(1020) and charged kaons with photons and nuclear targets. The kaon-proton scattering occurs at energies far above those available elsewhere. We present the first measurement of coherent photoproduction of K^{+}K^{-} pairs on lead ions in ultraperipheral collisions using the ALICE detector, including the first investigation of direct K^{+}K^{-} production. There is significant K^{+}K^{-} production at low transverse momentum, consistent with coherent photoproduction on lead targets. In the mass range 1.1

Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

First Measurement of the |t| Dependence of Incoherent J/ψ Photonuclear Production.

The first measurement of the cross section for incoherent photonuclear production of J/ψ vector mesons as a function of the Mandelstam |t| variable is presented. The measurement was carried out with the ALICE detector at midrapidity, |y|<0.8, using ultraperipheral collisions of Pb nuclei at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02 TeV. This rapidity interval corresponds to a Bjorken-x range (0.3-1.4)×10^{-3}. Cross sections are given in five |t| intervals in the range 0.04<|t|<1 GeV^{2} and compared to the predictions by different models. Models that ignore quantum fluctuations of the gluon density in the colliding hadron predict a |t| dependence of the cross section much steeper than in data. The inclusion of such fluctuations in the same models provides a better description of the data.

The Clinical and Economic Impact of Delayed Reperfusion Therapy: Real-World Evidence. / O Impacto Clínico e Econômico do Atraso na Terapia de Reperfusão: Evidências do Mundo Real.

BACKGROUND: Early reperfusion therapy is acknowledged as the most effective approach for reducing case fatality rates in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVE: Estimate the clinical and economic consequences of delaying reperfusion in patients with STEMI. METHODS: This retrospective cohort study evaluated mortality rates and the total expenses incurred by delaying reperfusion therapy among 2622 individuals with STEMI. Costs of in-hospital care and lost productivity due to death or disability were estimated from the perspective of the Brazilian Unified Health System indexed in international dollars (Int$) adjusted by purchase power parity. A p < 0.05 was considered statistically significant. RESULTS: Each additional hour of delay in reperfusion therapy was associated with a 6.2% increase (95% CI: 0.3% to 11.8%, p = 0.032) in the risk of in-hospital mortality. The overall expenses were 45% higher among individuals who received treatment after 9 hours compared to those who were treated within the first 3 hours, primarily driven by in-hospital costs (p = 0.005). A multivariate linear regression model indicated that for every 3-hour delay in thrombolysis, there was an increase in in-hospital costs of Int$497 ± 286 (p = 0.003). CONCLUSIONS: The findings of our study offer further evidence that emphasizes the crucial role of prompt reperfusion therapy in saving lives and preserving public health resources. These results underscore the urgent need for implementing a network to manage STEMI cases.

FUNDAMENTO: A terapia de reperfusão precoce é reconhecida como a abordagem mais eficaz para reduzir as taxas de letalidade de casos em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). OBJETIVO: Estimar as consequências clínicas e econômicas do atraso da reperfusão em pacientes com IAMCSST. MÉTODOS: O presente estudo de coorte retrospectivo avaliou as taxas de mortalidade e as despesas totais decorrentes do atraso na terapia de reperfusão em 2.622 indivíduos com IAMCSST. Os custos de cuidados hospitalares e perda de produtividade por morte ou incapacidade foram estimados sob a perspectiva do Sistema Único de Saúde indexado em dólares internacionais (Int$) ajustados pela paridade do poder de compra. Foi considerado estatisticamente significativo p < 0,05. RESULTADOS: Cada hora adicional de atraso na terapia de reperfusão foi associada a um aumento de 6,2% (intervalo de confiança de 95%: 0,3% a 11,8%, p = 0,032) no risco de mortalidade hospitalar. As despesas gerais foram 45% maiores entre os indivíduos que receberam tratamento após 9 horas em comparação com aqueles que foram tratados nas primeiras 3 horas, impulsionados principalmente pelos custos hospitalares (p = 0,005). Um modelo de regressão linear multivariada indicou que para cada 3 horas de atraso na trombólise, houve um aumento nos custos hospitalares de Int$ 497 ± 286 (p = 0,003). CONCLUSÕES: Os achados do nosso estudo oferecem mais evidências que enfatizam o papel crucial da terapia de reperfusão imediata no salvamento de vidas e na preservação dos recursos de saúde pública. Estes resultados enfatizam a necessidade urgente de implementação de uma rede para gerir casos de IAMCSST.

Emergence of Long-Range Angular Correlations in Low-Multiplicity Proton-Proton Collisions.

This Letter presents the measurement of near-side associated per-trigger yields, denoted ridge yields, from the analysis of angular correlations of charged hadrons in proton-proton collisions at sqrt[s]=13 TeV. Long-range ridge yields are extracted for pairs of charged particles with a pseudorapidity difference of 1.4<|Δη|<1.8 and a transverse momentum of 1

Dialysis parameters associated with SARS-CoV-2 infection and prognosis in end-stage kidney disease.

BACKGROUND: The Covid-19 pandemic has affected patients with end-stage kidney disease (ESKD). Whether dialysis parameters have a prognostic value in ESKD patients with Covid-19 remains unclear. MATERIALS AND METHODS: We retrospectively evaluated clinical characteristics, blood pressure (BP) and dialysis parameters in ESKD patients undergoing maintenance outpatient hemodialysis, with (Covid-ESKD) and without (No-Covid-ESKD) Covid-19, at four Brazilian hemodialysis facilities. The Covid-ESKD (n = 107; 54% females; 60.8 ± 17.7 years) and No-Covid-ESKD (n = 107; 62% females; 58.4 ± 14.6 years) groups were matched by calendar time. The average BP and dialysis parameters were calculated during the pre-infection, acute infection, and post-infection periods. The main outcomes were Covid-19 hospitalization and all-cause mortality. RESULTS: Covid-ESKD patients had greater intradialytic and postdialysis systolic BP and lower predialysis weight, postdialysis weight, ultrafiltration rate, and interdialytic weight gain during acute-illness compared to 1-week-before-illness, while these changes were not observed in No-Covid-ESKD patients. After 286 days of follow-up (range, 276-591), there were 18 Covid-19-related hospitalizations and 28 deaths among Covid-ESKD patients. Multivariable logistic regression analysis showed that increases in predialysis systolic BP from 1-week-before-illness to acute-illness (OR, 95%CI = 1.06, 1.02-1.10; p = .004) and Covid-19 vaccination (OR, 95%CI = 0.16, 0.04-0.69; p = .014) were associated with hospitalization in Covid-ESKD patients. Multivariable Cox-regression analysis showed that Covid-19-related hospitalization (HR, 95%CI = 5.17, 2.07-12.96; p < .001) and age (HR, 95%CI = 1.05, 1.01-1.08; p = .008) were independent predictors of all-cause mortality in Covid-ESKD patients. CONCLUSION: Acute Covid-19 illness is associated with variations in dialysis parameters of volume status in patients with ESKD. Furthermore, increases in predialysis BP during acute Covid-19 illness are associated with an adverse prognosis in Covid-ESKD patients.

Dialysis parameters were influenced by SARS-CoV-2 infection and may have prognostic value in patients with Covid-19.Increases in blood pressure during acute Covid-19 illness and the lack of vaccination for Covid-19 were predictors of hospitalization for Covid-19.Hospitalization for Covid-19 and age were independent risk factors for all-cause death.

Cellulose Nanocrystals Show Anti-Adherent and Anti-Biofilm Properties against Oral Microorganisms.

Cellulose nanocrystals (CNCs) are cellulose-derived nanomaterials that can be easily obtained, e.g., from vegetable waste produced by circular economies. They show promising antimicrobial activity and an absence of side effects and toxicity. This study investigated the ability of CNCs to reduce microbial adherence and biofilm formation using in vitro microbiological models reproducing the oral environment. Microbial adherence by microbial strains of oral interest, Streptococcus mutans and Candida albicans, was evaluated on the surfaces of salivary pellicle-coated enamel disks in the presence of different aqueous solutions of CNCs. The anti-biofilm activity of the same CNC solutions was tested against S. mutans and an oral microcosm model based on mixed plaque inoculum using a continuous-flow bioreactor. Results showed the excellent anti-adherent activity of the CNCs against the tested strains from the lowest concentration tested (0.032 wt. %, p < 0.001). Such activity was significantly higher against S. mutans than against C. albicans (p < 0.01), suggesting a selective anti-adherent activity against pathogenic strains. At the same time, there was a minimal, albeit significant, anti-biofilm activity (0.5 and 4 wt. % CNC solution for S. mutans and oral microcosm, respectively, p = 0.01). This makes CNCs particularly interesting as anticaries agents, encouraging their use in the oral field.

Gene-Environment Interactions in Irrational Beliefs: The Roles of Childhood Adversity and Multiple Candidate Genes.

Cognitive behavioral therapy is based on the view that maladaptive thinking is the causal mechanism of mental disorders. While this view is supported by extensive evidence, very limited work has addressed the factors that contribute to the development of maladaptive thinking. The present study aimed to uncover interactions between childhood maltreatment and multiple genetic differences in irrational beliefs. Childhood maltreatment and irrational beliefs were assessed using multiple self-report instruments in a sample of healthy volunteers (N = 452). Eighteen single-nucleotide polymorphisms were genotyped in six candidate genes related to neurotransmitter function (COMT; SLC6A4; OXTR), neurotrophic factors (BDNF), and the hypothalamic-pituitary-adrenal axis (NR3C1; CRHR1). Gene-environment interactions (G×E) were first explored in models that employed one measure of childhood maltreatment and one measure of irrational beliefs. These effects were then followed up in models in which either the childhood maltreatment measure, the irrational belief measure, or both were substituted by parallel measures. Consistent results across models indicated that childhood maltreatment was positively associated with irrational beliefs, and these relations were significantly influenced by COMT rs165774 and OXTR rs53576. These results remain preliminary until independent replication, but they represent the best available evidence to date on G×E in a fundamental mechanism of psychopathology.

The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis.

BACKGROUND: Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus. METHODS: Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects. RESULTS: Five studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low. CONCLUSIONS: Within this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable. TRIAL REGISTRATION: PROSPERO identifier: CRD42023393020.

Deep Aramaic: Towards a synthetic data paradigm enabling machine learning in epigraphy.

Epigraphy is witnessing a growing integration of artificial intelligence, notably through its subfield of machine learning (ML), especially in tasks like extracting insights from ancient inscriptions. However, scarce labeled data for training ML algorithms severely limits current techniques, especially for ancient scripts like Old Aramaic. Our research pioneers an innovative methodology for generating synthetic training data tailored to Old Aramaic letters. Our pipeline synthesizes photo-realistic Aramaic letter datasets, incorporating textural features, lighting, damage, and augmentations to mimic real-world inscription diversity. Despite minimal real examples, we engineer a dataset of 250 000 training and 25 000 validation images covering the 22 letter classes in the Aramaic alphabet. This comprehensive corpus provides a robust volume of data for training a residual neural network (ResNet) to classify highly degraded Aramaic letters. The ResNet model demonstrates 95% accuracy in classifying real images from the 8th century BCE Hadad statue inscription. Additional experiments validate performance on varying materials and styles, proving effective generalization. Our results validate the model's capabilities in handling diverse real-world scenarios, proving the viability of our synthetic data approach and avoiding the dependence on scarce training data that has constrained epigraphic analysis. Our innovative framework elevates interpretation accuracy on damaged inscriptions, thus enhancing knowledge extraction from these historical resources.

Effect of Empagliflozin with or without the Addition of Evolocumab on HDL Subspecies in Individuals with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the EXCEED-BHS3 Trial.

Evolocumab and empagliflozin yield a modest rise in plasma high-density lipoprotein cholesterol (HDL-C) through unknown mechanisms. This study aims to assess the effect of evolocumab plus empagliflozin vs. empagliflozin alone on HDL subspecies isolated from individuals with type 2 diabetes mellitus (T2D). This post hoc prespecified analysis of the EXCEED-BHS3 trial compared the effects of a 16-week therapy with empagliflozin (E) alone or in combination with evolocumab (EE) on the lipid profile and cholesterol content in HDL subspecies in individuals with T2D divided equally into two groups of 55 patients. Both treatments modestly increased HDL-C. The cholesterol content in HDL subspecies 2a (7.3%), 3a (7.2%) and 3c (15%) increased from baseline in the E group, while the EE group presented an increase from baseline in 3a (9.3%), 3b (16%) and 3c (25%). The increase in HDL 3b and 3c was higher in the EE group when compared to the E group (p < 0.05). No significant interactive association was observed between changes in hematocrit and HDL-C levels after treatment. Over a 16-week period, empagliflozin with or without the addition of evolocumab led to a modest but significant increase in HDL-C. The rise in smaller-sized HDL particles was heterogeneous amongst the treatment combinations.

Guidelines on the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ­ 2024 / Diretriz sobre Diagnóstico e Tratamento da Cardiomiopatia Hipertrófica ­ 2024

Hypertrophic cardiomyopathy (HCM) is a form of genetically caused heart muscle disease, characterized by the thickening of the ventricular walls. Diagnosis requires detection through imaging methods (Echocardiogram or Cardiac Magnetic Resonance) showing any segment of the left ventricular wall with a thickness > 15 mm, without any other probable cause. Genetic analysis allows the identification of mutations in genes encoding different structures of the sarcomere responsible for the development of HCM in about 60% of cases, enabling screening of family members and genetic counseling, as an important part of patient and family management. Several concepts about HCM have recently been reviewed, including its prevalence of 1 in 250 individuals, hence not a rare but rather underdiagnosed disease. The vast majority of patients are asymptomatic. In symptomatic cases, obstruction of the left ventricular outflow tract (LVOT) is the primary disorder responsible for symptoms, and its presence should be investigated in all cases. In those where resting echocardiogram or Valsalva maneuver does not detect significant intraventricular gradient (> 30 mmHg), they should undergo stress echocardiography to detect LVOT obstruction. Patients with limiting symptoms and severe LVOT obstruction, refractory to beta-blockers and verapamil, should receive septal reduction therapies or use new drugs inhibiting cardiac myosin. Finally, appropriately identified patients at increased risk of sudden death may receive prophylactic measure with implantable cardioverter-defibrillator (ICD) implantation.

La miocardiopatía hipertrófica (MCH) es una forma de enfermedad cardíaca de origen genético, caracterizada por el engrosamiento de las paredes ventriculares. El diagnóstico requiere la detección mediante métodos de imagen (Ecocardiograma o Resonancia Magnética Cardíaca) que muestren algún segmento de la pared ventricular izquierda con un grosor > 15 mm, sin otra causa probable. El análisis genético permite identificar mutaciones en genes que codifican diferentes estructuras del sarcómero responsables del desarrollo de la MCH en aproximadamente el 60% de los casos, lo que permite el tamizaje de familiares y el asesoramiento genético, como parte importante del manejo de pacientes y familiares. Varios conceptos sobre la MCH han sido revisados recientemente, incluida su prevalencia de 1 entre 250 individuos, por lo tanto, no es una enfermedad rara, sino subdiagnosticada. La gran mayoría de los pacientes son asintomáticos. En los casos sintomáticos, la obstrucción del tracto de salida ventricular izquierdo (TSVI) es el trastorno principal responsable de los síntomas, y su presencia debe investigarse en todos los casos. En aquellos en los que el ecocardiograma en reposo o la maniobra de Valsalva no detecta un gradiente intraventricular significativo (> 30 mmHg), deben someterse a ecocardiografía de esfuerzo para detectar la obstrucción del TSVI. Los pacientes con síntomas limitantes y obstrucción grave del TSVI, refractarios al uso de betabloqueantes y verapamilo, deben recibir terapias de reducción septal o usar nuevos medicamentos inhibidores de la miosina cardíaca. Finalmente, los pacientes adecuadamente identificados con un riesgo aumentado de muerte súbita pueden recibir medidas profilácticas con el implante de un cardioversor-desfibrilador implantable (CDI).

A cardiomiopatia hipertrófica (CMH) é uma forma de doença do músculo cardíaco de causa genética, caracterizada pela hipertrofia das paredes ventriculares. O diagnóstico requer detecção por métodos de imagem (Ecocardiograma ou Ressonância Magnética Cardíaca) de qualquer segmento da parede do ventrículo esquerdo com espessura > 15 mm, sem outra causa provável. A análise genética permite identificar mutações de genes codificantes de diferentes estruturas do sarcômero responsáveis pelo desenvolvimento da CMH em cerca de 60% dos casos, permitindo o rastreio de familiares e aconselhamento genético, como parte importante do manejo dos pacientes e familiares. Vários conceitos sobre a CMH foram recentemente revistos, incluindo sua prevalência de 1 em 250 indivíduos, não sendo, portanto, uma doença rara, mas subdiagnosticada. A vasta maioria dos pacientes é assintomática. Naqueles sintomáticos, a obstrução do trato de saída do ventrículo esquerdo (OTSVE) é o principal distúrbio responsável pelos sintomas, devendo-se investigar a sua presença em todos os casos. Naqueles em que o ecocardiograma em repouso ou com Manobra de Valsalva não detecta gradiente intraventricular significativo (> 30 mmHg), devem ser submetidos à ecocardiografia com esforço físico para detecção da OTSVE.   Pacientes com sintomas limitantes e grave OTSVE, refratários ao uso de betabloqueadores e verapamil, devem receber terapias de redução septal ou uso de novas drogas inibidoras da miosina cardíaca. Por fim, os pacientes adequadamente identificados com risco aumentado de morta súbita podem receber medida profilática com implante de cardiodesfibrilador implantável (CDI).

Natural, biphasic calcium phosphate from fish bones for enamel remineralization and dentin tubules occlusion.

OBJECTIVES: A calcium phosphate extracted from fish bones (CaP-N) was evaluated for enamel remineralization and dentinal tubules occlusion. METHODS: CaP-N was characterized by assessing morphology by SEM, crystallinity by PXRD, and composition by ICP-OES. CaP-N morphology, crystallinity, ion release, and pH changes over time in neutral and acidic solutions were studied. CaP-N was then tested to assess remineralization and dentinal tubules occlusion on demineralized human enamel and dentin specimens (n = 6). Synthetic calcium phosphate in form of stoichiometric hydroxyapatite nanoparticles (CaP-S) and tap water were positive and negative controls, respectively. After treatment (brush every 12 h for 5d and storage in Dulbecco's modified PBS), specimens' morphology and surface composition were assessed (by SEM-EDS), while the viscoelastic behavior was evaluated with microindentation and DMA. RESULTS: CaP-N consisted of rounded microparticles (200 nm - 1 µm) composed of 33 wt% hydroxyapatite and 67 wt% ß-tricalcium phosphate. In acidic solution, CaP-N released calcium and phosphate ions thanks to the preferential ß-tricalcium phosphate phase dissolution. Enamel remineralization was induced by CaP-N comparably to CaP-S, while CaP-N exhibited a superior dentinal tubule occlusion than CaP-S, forming mineral plugs and depositing new nanoparticles onto demineralized collagen. This behavior was attributed to its bigger particle size and increased solubility. DMA depth profiling and SEM showed an excellent interaction between the newly formed mineralized structures and the pristine tissue, particularly at the exposed collagen fibrils. SIGNIFICANCE: CaP-N demonstrated very good remineralizing and occlusive activity in vitro, comparable to CaP-S, thus could be a promising circular economy alternative therapeutic agent for dentistry.