Miracle-dz/UniFAR-FTUs huggingface dataset:
Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos

Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.
High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management

Objective To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. Data Sources PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords “semaglutide” and “obesity,” “weight,” “high dose,” “high-dose,” or “2.4. ” Study Selection and Data Extraction Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. Data Synthesis Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. Relevance to Patient Care and Clinical Practice High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. Conclusions High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.
Labeling of Nanofiber-Forming Peptides by Site-Directed Bioconjugation: Effect of Spacer Length on Self-Assembly.

BACKGROUND The conjugation of small organic molecules to self-assembling peptides is a versatile tool to decorate nanostructures with original functionalities. Labeling with chromophores or fluorophores, for example, creates optically active fibers with potential interest in photonic devices. AIM AND OBJECTIVE In this work, we present a rapid and effective labeling procedure for a self-assembling peptide able to form nanofibers. Rapid periodate oxidation of the N-terminal serine residue of the peptide and subsequent conjugation with dansyl moiety generated fluorophore-decorated peptides. RESULTS Three dansyl-conjugated self-assembling peptides with variable spacer-length were synthesized and characterized and the role of the size of the linker between fluorophore and peptide in self-assembling was investigated. Our results show that a short linker can alter the self-assembly in nanofibers of the peptide. CONCLUSIONS Herein we report on an alternative strategy for creating functionalized nanofibrils, able to expand the toolkit of chemoselective bioconjugation strategies to be used in site-specific decoration of self-assembling peptides.
Implantation of ventricular assist devices in hypertrophic cardiomyopathy with left ventricular systolic dysfunction

The outcomes of patients with hypertrophic cardiomyopathy with left ventricular systolic dysfunction (HCM‐LVSD) undergoing left ventricular assist device (LVAD) implantation remain unclear. We retrospectively evaluated the clinical impact of LVAD implantation on clinical outcomes, including haemodynamics and brain natriuretic peptide (BNP) levels, in patients with HCM‐LVSD, in comparison with those with dilated cardiomyopathy (DCM).
Kinetics of manganese leaching from an iron-rich manganese dioxide ore with bagasse pith as a reductant

The kinetics of reductive leaching of manganese from iron-rich manganese dioxide ore (IRMDO) using bagasse pith as a reductant in the presence of sulfuric acid was investigated. The effects of reductant type, stirring speed, ore particle size, leaching temperature, sulfuric acid concentration and weight ratio of IRMDO to bagasse pith on the leaching efficiency of manganese were studied. The experimental results indicated that an increase in temperature, sulphuric acid concentration and dosage of bagasse pith significantly enhanced the leaching efficiency of manganese, but manganese leaching efficiency increased with the decrease of the particle size of the ore. A leaching efficiency of 97% for total Mn was obtained under the following optimized conditions: 700 rpm of stirring rate, 10 : 5 of IRMDO to bagasse pith weight ratio, 4.78 mol L−1 of sulfuric acid concentration, 368 K of leaching temperature and 150 min of reaction time. The leaching efficiency of manganese based on the shrinking core model was found to be controlled by a surface chemical reaction. The apparent activation energy of the chemical reaction was 50.53 kJ mol−1, while the reaction was found to be of 0.94 and 0.36 order in terms of sulfuric acid and bagasse pith concentration, respectively. In addition, the decomposition mechanism of bagasse pith was investigated. The microstructures of the manganese oxide ores in pre- and post-leaching reactions were further studied by SEM and XRD analysis.
Impact of Albumin-to-Creatinine Ratio Point-of-Care Testing on the Diagnosis and Management of Diabetic Kidney Disease

Background: For the diagnosis of diabetic kidney disease (DKD), quantitative albuminuria measurement using the albumin-to-creatinine ratio (ACR) is recommended according to various guidelines. It can be measured either in specialized laboratories or using ACR point-of-care testing (POCT). This observational study aims at evaluating the effect of ACR POCT utilization on the DKD diagnosis and treatment management for glycemic control and blood pressure. Method: Data of 717 patients with diabetes (type 1 diabetes: n = 236; type 2 diabetes: n = 463; other diabetes forms: n = 18) were assessed in three centers. The impact of ACR POCT on DKD diagnosis and treatment management for glycemic control and blood pressure was assessed using a case report form. The assessment of ACR POCT utilization purpose and relevance for physicians was documented using a questionnaire. Results: Of all participants (n = 717), 39.1% had a confirmed/suspected DKD diagnosis. Hereof, 8.6% were newly diagnosed with DKD, and 9.9% were suspected with DKD based on the actual ACR POCT values. Within the group of patients with confirmed/suspected DKD (n = 280), treatment modification was performed in 46.1% of participants. A drug initiation with GLP-1 receptor agonists or SGLT2 inhibitors was performed in 11.1% or 8.9% of patients with confirmed/suspected DKD, respectively. Regarding the utilization purposes of ACR POCT, 100% of the physicians (n = 8) indicated using it to examine patients with diabetes with or without hypertension; 75% considered it very important for patients with diabetes. Conclusions: The implementation of ACR POCT may positively affect DKD diagnosis and subsequently allow better management of patients with diabetes.
Turkish validity and reliability of the COVERS pain scale.

OBJECTIVE The objective of this study is to determine the Turkish validity and reliability of COVERS. METHODS This study was conducted on 41 newborns as methodological design. The scales, such as newborn information form, COVERS, preterm infant pain profile (PIPP), and neonatal infant pain scale (NIPS), were used in the study. Validity (e.g., language, content concurrent, and construct) and internal consistency and inter-rater reliability of the scale were conducted. RESULTS It was found that COVERS showed a high correlation with PIPP and NIPS, and the item-total correlation of COVERS was above 0.30 during and after heel lance procedure. The Cronbach's α values were 0.77 and 0.83 during and after heel lance procedure, respectively. The kappa values of the items of COVERS were between 0.38 and 0.78 during heel lance procedure. CONCLUSIONS It was concluded in this study that there was a moderate correlation in intraclass correlation coefficients for scores of COVERS during both diaper change and heel lance procedures. It has been concluded that the scale is valid and reliable in 27-week-old and older newborns.
The network structure affects the fixation probability when it couples to the birth-death dynamics in finite population

The study of evolutionary dynamics on graphs is an interesting topic for researchers in various fields of science and mathematics. In systems with finite population, different model dynamics are distinguished by their effects on two important quantities: fixation probability and fixation time. The isothermal theorem declares that the fixation probability is the same for a wide range of graphs and it only depends on the population size. This has also been proved for more complex graphs that are called complex networks. In this work, we propose a model that couples the population dynamics to the network structure and show that in this case, the isothermal theorem is being violated. In our model the death rate of a mutant depends on its number of neighbors, and neutral drift holds only in the average. We investigate the fixation probability behavior in terms of the complexity parameter, such as the scale-free exponent for the scale-free network and the rewiring probability for the small-world network.
Elevated Aortic Pulse Wave Velocity Relates to Longitudinal Gray and White Matter Changes

Supplemental Digital Content is available in the text. Objective: To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years. Approach and Results: Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included T1-weighted imaging for quantifying gray matter volumes and T2-weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, cognitive diagnosis, Framingham stroke risk profile, APOE (apolipoprotein E)-ε4 carrier status, and intracranial volume. Two hundred seventy-eight participants (73±7 years, 58% male, 87% self-identified as non-Hispanic White, 159 with normal cognition, and 119 with mild cognitive impairment) from the Vanderbilt Memory & Aging Project (n=335) were followed on average for 4.9±1.6 years with PWV measurements occurring from September 2012 to November 2014 and longitudinal brain magnetic resonance imaging measurements occurring from September 2012 to June 2021. Higher baseline aortic PWV was related to greater decrease in hippocampal (β=−3.6 [mm3/y]/[m/s]; [95% CI, −7.2 to −0.02] P=0.049) and occipital lobe (β=−34.2 [mm3/y]/[m/s]; [95% CI, −67.8 to −0.55] P=0.046) gray matter volume over time. Higher baseline aortic PWV was related to greater increase in WMH volume over time in the temporal lobe (β=17.0 [mm3/y]/[m/s]; [95% CI, 7.2–26.9] P<0.001). All associations may be driven by outliers. Conclusions: In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.
Beneficial Effects of Cardiomyopathy-Associated Genetic Variants on Physical Performance: A Hypothesis-Generating Scoping Review

Background: Genetic variants associated with cardiomyopathies (CMPs) are prevalent in the general population. In young athletes, CMPs account for roughly a quarter of sudden cardiac death, with further unexplained clustering in specific sports. Consequently, most CMPs form a contraindication for competitive sports. We hypothesized that genetic variants might (paradoxically) improve physical performance early in life while impairing cardiac function later in life. Methods: Systematic PubMed search was done to investigate whether genetic variants in genes associated with CMPs could be related to beneficial performance phenotypes. Summary: In a limited number of studies (n = 6), 2,860 individuals/subjects with genetic variants were able to outperform those without said variants, as measured by running speed (∼38 m/min in heterozygous [HET] mice, n = 6, vs. ∼32 m/min in wild type [WT] mice, n = 7, p = 0.004) and distance (966 ± 169 km HET mice vs. 561 ± 144 km WT mice, p = 0.0035, n = 10), elite athlete status in endurance athletes (n = 1,672, p = 1.43 × 10−8), maximal oxygen uptake in elite athletes (absolute difference not provided, n = 32, p = 0.005), maximal oxygen uptake in unrelated individuals (n = 473, p = 0.0025), personal records in highly trained marathon runners (2:26:28 ± 0:06:23 min HET, n = 32, vs. 2:28:53 ± 0:05:50 min without polymorphism, n = 108, p = 0.020), and peripheral muscle force contraction in patients following a cardiac rehabilitation program (absolute values not provided, n = 260). Key Message: Beneficial effects in genetic variants associated with CMPs could hypothetically play a role in the selection of young athletes, consequently explaining the prevalence of such genetic variants in athletes and the general population.
Characterization of M116.1p, a Murine Cytomegalovirus Protein Required for Efficient Infection of Mononuclear Phagocytes

Human cytomegalovirus (HCMV) is a species-specific herpesvirus that causes severe disease in immunocompromised individuals and immunologically immature neonates. Murine cytomegalovirus (MCMV) is biologically similar to HCMV, and it serves as a widely used model for studying the infection, pathogenesis, and immune responses to HCMV. ABSTRACT Broad tissue tropism of cytomegaloviruses (CMVs) is facilitated by different glycoprotein entry complexes, which are conserved between human CMV (HCMV) and murine CMV (MCMV). Among the wide array of cell types susceptible to the infection, mononuclear phagocytes (MNPs) play a unique role in the pathogenesis of the infection as they contribute both to the virus spread and immune control. CMVs have dedicated numerous genes for the efficient infection and evasion of macrophages and dendritic cells. In this study, we have characterized the properties and function of M116, a previously poorly described but highly transcribed MCMV gene region that encodes M116.1p, a novel protein necessary for the efficient infection of MNPs and viral spread in vivo. Our study further revealed that M116.1p shares similarities with its positional homologs in HCMV and RCMV, UL116 and R116, respectively, such as late kinetics of expression, N-glycosylation, localization to the virion assembly compartment, and interaction with gH—a member of the CMVs fusion complex. This study, therefore, expands our knowledge about virally encoded glycoproteins that play important roles in viral infectivity and tropism. IMPORTANCE Human cytomegalovirus (HCMV) is a species-specific herpesvirus that causes severe disease in immunocompromised individuals and immunologically immature neonates. Murine cytomegalovirus (MCMV) is biologically similar to HCMV, and it serves as a widely used model for studying the infection, pathogenesis, and immune responses to HCMV. In our previous work, we have identified the M116 ORF as one of the most extensively transcribed regions of the MCMV genome without an assigned function. This study shows that the M116 locus codes for a novel protein, M116.1p, which shares similarities with UL116 and R116 in HCMV and RCMV, respectively, and is required for the efficient infection of mononuclear phagocytes and virus spread in vivo. Furthermore, this study establishes the α-M116 monoclonal antibody and MCMV mutants lacking M116, generated in this work, as valuable tools for studying the role of macrophages and dendritic cells in limiting CMV infection following different MCMV administration routes.
Atualização da Diretriz Brasileira de Hipercolesterolemia Familiar – 2021

Autores da Atualização: Maria Cristina de Oliveira Izar,1 Viviane Zorzanelli Rocha Giraldez,2,3 Adriana Bertolami,4 Raul Dias dos Santos Filho,5 Ana Maria Lottenberg,6,7 Marcelo Heitor Vieira Assad,8 José Francisco Kerr Saraiva,9 Ana Paula M. Chacra,2 Tania L. R. Martinez,10 Luciana Ribeiro Bahia,11 Francisco Antonio Helfenstein Fonseca,1 Andre Arpad Faludi,4 Andrei C. Sposito,12 Antônio Carlos Palandri Chagas,13 Cinthia Elim Jannes,2 Cristiane Kovacs Amaral,4 Daniel Branco de Araújo,4 Dennys Esper Cintra,12 Elaine dos Reis Coutinho,14 Fernando Cesena,15 Hermes Toros Xavier,16 Isabela Cardoso Pimentel Mota,4 Isabela de Carlos Back Giuliano,17 José Rocha Faria Neto,18 Juliana Tieko Kato,1 Marcelo Chiara Bertolami,4 Marcio Hiroshi Miname,2 Maria Helane Costa Gurgel Castelo,19,20,21 Maria Sílvia Ferrari Lavrador,6 Roberta Marcondes Machado,7 Patrícia Guedes de Souza,22 Renato Jorge Alves,23 Valeria Arruda Machado,1 Wilson Salgado Filho2
Silicon Resorption from Equisetum arvense Tea – A Randomized, Three-Armed Pilot Study

Abstract Equisetum arvense tea (TEA) contains high concentrations of silicon and has been used in folk medicine for the treatment of inflammatory ailments. We examined the resorption of silicon after TEA consumption. Safety and immunological effects were secondary outcomes. A monocentric, randomized, three-armed pilot study was conducted with 12 voluntary, healthy, male subjects. The study is registered in the German register for clinical trials (DRKS-ID: DRKS00016628). After a low silicon diet for 36 hours, 1000 mL TEA1 with approximately 200 000 µg silicon/L, TEA2 with approximately 750 000 µg silicon/L, or Si-low-Water (approximately 10 – 10 000 µg silicon/L as a control) were ingested on three consecutive days. Blood and urine samples were collected at baseline, day 1 examining silicon kinetics, day 3 examining silicon accumulation, and day 8 (safety, immunological parameters). Si-low-Water intake did not change silicon serum (Cmax 294 µg/L) or urine (19 000 µg/24 h) concentrations compared to baseline. Cmax was 2855 µg/L for TEA1 and 2498 µg/L for TEA2; tmax was 60 and 120 min, respectively. Silicon accumulation did not occur. Urine silica within 24 h (E24 h) was higher after TEA2 compared to TEA1 ingestion (142 000 vs. 109 000 µg/24 h). Serum silicon levels at t = 120 min differed significantly after intake of TEA2 or intake of Si-low-Water (p = 0.029). The immunological parameters did not show any significant changes indicating immunosuppressive effects in volunteers. TEA1 was well tolerated, while TEA2 caused diarrhoea in 4 subjects. Our investigations show that intake of TEA1 leads to significant rise in serum silicon concentration.
Microtubule dynamics influence the retrograde biased motility of kinesin-4 motor teams in neuronal dendrites

Microtubules establish the directionality of intracellular transport by kinesins and dynein through polarized assembly, but it remains unclear how directed transport occurs along microtubules organized with mixed polarity. We investigated the ability of the plus end–directed kinesin-4 motor KIF21B to navigate mixed polarity microtubules in mammalian dendrites. Reconstitution assays with recombinant KIF21B and engineered microtubule bundles or extracted neuronal cytoskeletons indicate that nucleotide-independent microtubule-binding regions of KIF21B modulate microtubule dynamics and promote directional switching on antiparallel microtubules. Optogenetic recruitment of KIF21B to organelles in live neurons induces unidirectional transport in axons but bidirectional transport with a net retrograde bias in dendrites. Removal of the secondary microtubule-binding regions of KIF21B or dampening of microtubule dynamics with low concentrations of nocodazole eliminates retrograde bias in live dendrites. Further exploration of the contribution of microtubule dynamics in dendrites to directionality revealed plus end–out microtubules to be more dynamic than plus end–in microtubules, with nocodazole preferentially stabilizing the plus end–out population. We propose a model in which both nucleotide-sensitive and -insensitive microtubule-binding sites of KIF21B motors contribute to the search and selection of stable plus end–in microtubules within the mixed polarity microtubule arrays characteristic of mammalian dendrites to achieve net retrograde movement of KIF21B-bound cargoes.