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OBJECTIVE: Although Brazil became the first country worldwide to ban the sale of all tobacco products with any additive that could alter their flavours and tastes in 2012, its implementation was effectively halted by tobacco industry lawsuits, including a constitutional challenge filed in the Federal Supreme Court in 2013. This study aimed at examining, for the first time in the country, the evolution over time of the new registrations of tobacco products with additives that would have been banned if not for the tobacco industry's interference ('counterfactual scenario'). METHODS: We used the newly available public database on the registration of tobacco products developed by the Health Regulatory Agency (from 2008 onwards). All types of tobacco products intended for the domestic market that contained 'banned additives in a counterfactual scenario' and were registered between January 1 and December 31 of each year were selected. RESULTS: Between 2012 and 2023, a total of 1112 new registrations of tobacco products with 'banned additives' were recorded. The spread of hookah tobacco registrations started in 2014, and by 2023, the cumulative incidence of registrations containing 'banned additives' was 641. Both manufactured cigarettes and hookah products reached their peaks in new registrations in 2020. CONCLUSIONS: After 12 years since the resolution intended to ban all additives that change the aroma and taste of tobacco products in Brazil, primarily to prevent smoking initiation, the tobacco industry's interference continues to successfully block its implementation. Countries facing similar challenges in tobacco control could consider generating comparable national data that might help expose the adverse impacts of tobacco industry interference on public health.

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OBJECTIVE: To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal defects, associated with a rare homozygous LMNA missense mutation (c.1579C>T). CASE DESCRIPTION: A 6-year-old girl was evaluated during hospitalization exhibiting the following dysmorphic signs: subtotal alopecia, dysmorphic facies with prominent eyes, marked micrognathia and retrognathia, small beaked nose, teeth crowding and thin lips, generalized lipodystrophy, narrow and sloping shoulders, generalized joint stiffness and bone reabsorption in the terminal phalanges. In dermatological examination, atrophic skin, loss of cutaneous elasticity, hyperkeratosis, dermal calcinosis, and hyperpigmented and hypochromic patches were observed. Radiology exams performed showed bilateral absence of the mandibular condyles, clavicle resorption with local amorphous bone mass confluence with the scapulae, shoulder joints with subluxation and severe bone dysplasia, hip dysplasia, osteopenia and subcutaneous calcifications. COMMENTS: MADA is a rare autosomal recessive disease caused by mutations in LMNA gene. It is characterized by craniofacial deformities, skeletal anomalies, skin alterations, lipodystrophy in certain regions of the body and premature ageing. Typical MADA is caused by the p.R527H mutation in the LMNA gene. However, molecular analysis performed from oral epithelial cells obtained from the patient showed the rare mutation c.1579C>T, p. R527C in the exon 9 of LMNA. This is the sixth family identified with this mutation described in the literature.

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Up to 25% of pediatric cataract cases are inherited. There is sparse information in the literature regarding the cost of whole-exome sequencing (WES) for suspected hereditary pediatric cataracts. Molecular diagnosis of suspected hereditary pediatric cataracts is important for comprehensive genetic counseling. We performed a partial economic evaluation with a mixed costing analysis, using reimbursement data and microcosting approach with a bottom-up technique to estimate the cost of using WES for genetic diagnosis of suspected hereditary pediatric cataracts from the perspective of the Brazilian governmental health care system. One hundred and ten participants from twenty-nine families in Rio de Janeiro (RJ) were included. Costs of consumables, staff and equipment were calculated. Two scenarios were created: (1) The reference scenario included patients from RJ with suspected hereditary pediatric cataracts plus two family members. (2) The alternative scenario considered other genetic diseases, resulting in 5,280 exams per month. Sensitivity analysis was also performed. In the reference scenario, the total cost per exam was 700.09 United States dollars (USD), and in the alternative scenario, the total cost was 559.23 USD. The cost of WES alone was 527.85 USD in the reference scenario and 386.98 USD in the alternative scenario. Sensitivity analysis revealed that the largest costs were associated with consumables in both scenarios. Economic evaluations can help inform policy decisions, especially in middle-income countries such as Brazil.

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BACKGROUND AND AIMS: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. METHODS: A national, multicenter, factorial, and parallel placebocontrolled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICAFH) þ phytosterol placebo þ krill oil placebo; 2) DICA-FH þ phytosterol 2 g/day þ krill oil placebo; 3) DICA-FH þ phytosterol placebo þ krill oil 2 g/day; or 4) DICA-FH þ phytosterol 2 g/day þ krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. RESULTS: A total of 58 participants were enrolled between May e August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. CONCLUSIONS: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

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We review the evidence for the presence of stem/progenitor cells in the heart and the preclinical and clinical data using diverse cell types for the therapy of cardiac diseases. We highlight the failure of adult stem/progenitor cells to ameliorate heart function in most cardiac diseases, with the possible exception of refractory angina. The use of pluripotent stem cell-derived cardiomyocytes is analysed as a viable alternative therapeutic option but still needs further research at preclinical and clinical stages. We also discuss the use of direct reprogramming of cardiac fibroblasts into cardiomyocytes and the use of extracellular vesicles as therapeutic agents in ischemic and non-ischemic cardiac diseases. Finally, gene therapies and genome editing for the treatment of hereditary cardiac diseases, ablation of genes responsible for atherosclerotic disease, or modulation of gene expression in the heart are discussed.

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Sarcopenia, a clinical syndrome primarily associated with reduced muscle mass in the elderly, has a negative impact on quality of life and survival. It can occur secondarily to other diseases such as heart failure (HF), a complex clinical syndrome with high morbidity and mortality. The simultaneous occurrence of these two conditions can worsen the prognosis of their carriers, especially in the most severe cases of HF, as in patients with reduced left ventricular ejection fraction (LVEF). However, due to the heterogeneous diagnostic criteria for sarcopenia, estimates of its prevalence present a wide variation, leading to new criteria having been recently proposed for its diagnosis, emphasizing muscle strength and function rather than skeletal muscle mass. The primary objective of this study is to evaluate the prevalence of sarcopenia and/or dynapenia in individuals with HF with reduced LVEF according to the most recent criteria, and compare the gene and protein expression of those patients with and without sarcopenia. The secondary objectives are to evaluate the association of sarcopenia and/or dynapenia with the risk of clinical events and death, quality of life, cardiorespiratory capacity, ventilatory efficiency, and respiratory muscle strength. The participants will answer questionnaires to evaluate sarcopenia and quality of life, and will undergo the following tests: handgrip strength, gait speed, dual-energy X-ray absorptiometry, respiratory muscle strength, cardiopulmonary exercise, as well as genomic and proteomic analysis, and dosage of N-terminal pro-B-type natriuretic peptide and growth differentiation factor-15. An association between sarcopenia and/or dynapenia with unfavorable clinical evolution is expected to be found, in addition to reduced quality of life, cardiorespiratory capacity, ventilatory efficiency, and respiratory muscle strength.

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ABSTRACT Objective: To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal defects, associated with a rare homozygous LMNA missense mutation (c.1579C>T). Case description: A 6-year-old girl was evaluated during hospitalization exhibiting the following dysmorphic signs: subtotal alopecia, dysmorphic facies with prominent eyes, marked micrognathia and retrognathia, small beaked nose, teeth crowding and thin lips, generalized lipodystrophy, narrow and sloping shoulders, generalized joint stiffness and bone reabsorption in the terminal phalanges. In dermatological examination, atrophic skin, loss of cutaneous elasticity, hyperkeratosis, dermal calcinosis, and hyperpigmented and hypochromic patches were observed. Radiology exams performed showed bilateral absence of the mandibular condyles, clavicle resorption with local amorphous bone mass confluence with the scapulae, shoulder joints with subluxation and severe bone dysplasia, hip dysplasia, osteopenia and subcutaneous calcifications. Comments: MADA is a rare autosomal recessive disease caused by mutations in LMNA gene. It is characterized by craniofacial deformities, skeletal anomalies, skin alterations, lipodystrophy in certain regions of the body and premature ageing. Typical MADA is caused by the p.R527H mutation in the LMNA gene. However, molecular analysis performed from oral epithelial cells obtained from the patient showed the rare mutation c.1579C>T, p. R527C in the exon 9 of LMNA. This is the sixth family identified with this mutation described in the literature.

RESUMO Objetivo: Relatar o caso de uma jovem que apresentava um fenótipo grave de displasia mandibuloacral tipo A (MADA) caracterizado por alterações osteolíticas proeminentes e defeitos ectodérmicos, associados a uma rara mutação homozigótica missense no gene LMNA (c.1579C>T). Descrição do caso: Uma menina de seis anos foi avaliada durante hospitalização apresentando os seguintes sinais dismórficos: alopecia subtotal, fácies dismórfica com olhos proeminentes, micrognatia e retrognatia acentuada, nariz pequeno e adunco, dentes apinhados e lábios finos, lipodistrofia generalizada, ombros estreitos e inclinados, rigidez articular e reabsorção óssea nas falanges terminais. Ao exame dermatológico, observou-se pele atrófica, perda da elasticidade cutânea, hiperceratose, calcinose dérmica e manchas hiperpigmentadas e hipocrômicas. Exames radiológicos realizados mostraram ausência de côndilos mandibulares bilaterais, reabsorção da clavícula com massa óssea amorfa local confluindo com as escápulas, articulações do ombro com subluxação e displasia óssea severa, com displasia coxofemoral, osteopenia e calcificações subcutâneas. Comentários: MADA é uma doença autossômica recessiva rara causada por mutações no gene LMNA. Caracteriza-se por deformidades craniofaciais, anomalias esqueléticas, alterações cutâneas, lipodistrofia em determinadas regiões do corpo e envelhecimento precoce. MADA típica é causada pela mutação p.R527H no gene LMNA. No entanto, a análise molecular realizada com células epiteliais orais obtidas da paciente mostrou a mutação rara c.1579C>T, p. R527C no exon 9 do gene LMNA. Esta é a sexta família identificada com essa mutação descrita na literatura.

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Social media platforms are a valuable source of data for investigating cultural and political trends related to public interest in nature and conservation. Here, we use the micro-blogging social network Twitter to explore trends in public interest in Brazilian protected areas (PAs). We identified ~400,000 Portuguese language tweets pertaining to all categories of Brazilian PAs over a ten-year period (1 January 2011-31 December 2020). We analysed the content of these tweets and calculated metrics of user engagement (likes and retweets) to uncover patterns and drivers of public interest in Brazilian PAs. Our results indicate that users / tweets mentioning PAs remained stable throughout the sample period. However, engagement with tweets grew steeply, particularly from 2018 onward and coinciding with a change in the Brazilian federal government. Furthermore, public interest was not evenly distributed across PAs; while national parks were the subject of the most tweets, mainly related to tourism activities, tweets related to conflicts among park users and managers were more likely to engage Twitter users. Our study highlights that automatic or semi-automatic monitoring of social media content and engagement has great potential as an early warning system to identify emerging conflicts and to generate data and metrics to support PA policy, governance and management.

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OBJECTIVE: To evaluate hip and knee muscular function, knee patient-reported outcome measures and hop performance in patients with a clinical indication for combined ACL+ALL reconstruction surgery compared to patients with an isolated ACL reconstruction surgery indication (preoperative phase) and to a control group. DESIGN: Cross-sectional study. METHODS: The sample was composed of male individuals, aged between 18 and 59 years, divided into three groups (ACL, ACL+ALL and Control). Isokinetic dynamometry was performed for the flexor and extensor knee muscles and for the hip abductors and adductors. SLHT, COHT and the Lysholm score were performed. Pain, swelling, and thigh trophism were also measured. RESULTS: The study participants were 89 male individuals: 63 in the injury group and 26 in the control group. After applying the criteria for an ALL reconstruction indication, 33 patients were assigned to the ACL Group and 30 patients to the ACL+ALL Group. Regarding knee and hip muscle function, both groups presented worse results when compared to the control group, however, did not show significant differences compared to each other. Regarding the functional variables, the ACL+ALL group showed a significantly shorter distance achieved in the Crossover Hop Test than the other groups, as well as more pain during the tests. CONCLUSION: Knee and hip muscular functions are impaired after an ACL injury and do not seem to be influenced or worsened in individuals with greater rotational instability with clinical indications for combined reconstruction of the anterior cruciate and the anterolateral ligaments of the knee.

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Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare, frequently misdiagnosed, autosomal dominant disease caused by mutations in the FTL gene. It causes bilateral pediatric cataract and hyperferritinemia without iron overload. The objective of this case series, describing three Brazilian families, is to increase awareness of HHCS, as well as to discuss possible phenotypic interactions with concurrent mutations in HFE, the gene associated with autosomal recessive inheritance hereditary hemochromatosis. Whole-exome sequencing was performed in eight individuals with HHCS from three different families, as well as one unaffected member from each family for trio analysis-a total of eleven individuals. Ophthalmological and clinical genetic evaluations were conducted. The likely pathogenic variant c.-157G>A in FTL was found in all affected individuals. They presented slowly progressing bilateral cataract symptoms before the age of 14, with a phenotype of varied bilateral diffuse opacities. Hyperferritinemia was present in all affected members, varying from 971 ng/mL to 4899 ng/mL. There were two affected individuals with one concurrent pathogenic variant in HFE (c.187C>G, p.H63D), who were also the ones with the highest values of serum ferritin in our cohort. Few publications describe individuals with pathogenic mutations in both FTL and HFE genes, and further studies are needed to assess possible phenotypic interactions causing higher values of hyperferritinemia.

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Advanced therapy products, considered special medications, require Anvisa approval for use and commercialization in Brazil. They include advanced cellular therapy products, tissue engineering products, and gene therapy products, which due to their complexity involve innovation and risks, optimized regulatory channels for their development and life cycle monitoring. The scientific elements and the compliance with applicable regulatory aspects are fundamental pillars for the advancement of clinical trials, the positive evidence of the benefit-risk profile, and the definition of the critical quality attributes, from the perspective of making safe, efficacy, and high-quality products available to the population. The approval models of these products in Brazil adapt to the specificities and characteristics of the technology and the patient target population, with accelerated regulatory analyses, use in emergency situations by risk controls and specific monitoring mechanisms, principally those related to rare diseases without other therapeutic alternatives. The opportune access to the advance therapy product with safety, efficacy, and quality involves innovative normative elements that include the long-term follow-up of the safety and efficacy and of the adaptive pharmacovigilance requisites, as well as the traceability mechanisms for starting materials, products, and patients.

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Objectives To verify the relationships between sleep duration (Total Sleep Time - TST) and postural control of female night workers before and after shift. As well as, to verify if there is an influence of the body mass index (BMI) on the postural control of these female workers before and after shift. Methods A total of 14 female night workers (mean age: 35.0 ± 7.7 years) were evaluated. An actigraph was placed on the wrist to evaluate the sleep-wake cycle. The body mass and height were measured, and BMI was calculated. Postural control was evaluated by means of a force platform, with eyes opened and eyes closed before and after the 12-hour workday. Results There was an effect of the BMI on the velocity and the center of pressure path with eyes opened before ( t = 2.55, p = 0.02) and after ( t = 4.10, p < 0.01) night work. The BMI impaired the velocity and the center of pressure path with eyes closed before ( t = 3.05, p = 0.01; t = 3.04, p = 0.01) and after ( t = 2.95, p = 0.01; t = 2.94, p = 0.01) night work. Furthermore, high BMI is associated with female workers' postural sway ( p < 0.05). Conclusion Therefore, high BMI impairs the postural control of female night workers, indicating postural instability before and after night work.

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Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.

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OBJECTIVES: To compare the effect of whitening toothpastes with different mechanisms of action on discolored teeth subjected to additional staining/or not. METHODS: One hundred twenty tooth specimens were stained for 14 days (staining broth under constant agitation and pH=7) and then allocated into the groups of toothpastes with different whitening ingredients (n=10): 1. Regular - Colgate Total 12 Clean Mint; 2. CLWI - Colgate Luminous White Instant (blue pigment); 3. CLWA - Colgate Luminous White Advanced Expert (hydrogen peroxide); 4. CLWAC - Colgate Luminous White Activated Charcoal (activated charcoal); 5. OB3D - Oral-B 3D WHITE Brilliant Fresh (abrasive); 6. TW - Teeth Whitening (charcoal powder). Specimens were submitted to two experimental models: A. Daily staining-toothbrush cycling: staining solution (5min), toothbrushing (45 strokes) and artificial saliva (3h), 2x/day, for 5 days; B. Only toothbrushing (30.000 brushing strokes). Color change was determined with a spectrophotometer (CIEDE2000 and Whiteness Index for Dentistry - WID) and statistically analyzed (α=0.05). RESULTS: For both models, ΔE00 and Δa did not differ significantly between the whitening toothpastes and the regular. All groups showed a decrease in tooth yellowness (-Δb) and an increase in WID. Group Teeth Whitening exhibited a decrease in luminosity (-ΔL). In model A, Groups did not differ significantly from the Regular in terms of ΔL (p=0.35) and Δb (p=0.74). Groups CLWI and OB3D exhibited a decrease in luminosity. Reduced redness (-Δa) occurred only in Group CLWI. In Model B, Groups OB3D (p=0.021) and CLWA (p=0.001) exhibited higher change in luminosity than in Group Teeth Whitening. All exhibited increased redness (+Δa) and lightness (+ΔL), except the Regular, CLWAC, and Teeth Whitening. Group OB3D had a significantly higher change in Δb than the Regular (p=0.021). CONCLUSIONS: Irrespective of the mechanism of action, all toothpastes reduced tooth yellowness and promoted similar overall color change. Exposure of the teeth to additional staining during the toothbrushing cycles did not influence the effect of the whitening toothpastes. CLINICAL SIGNIFICANCE: Whitening toothpastes should be tested in conditions that more closely simulate their use in a clinical scenario, in which alternate cycles of staining and brushing occur on a daily basis. However, even in such conditions, they were unable to promote a color change that differed from that of a regular toothpaste.

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STATEMENT OF PROBLEM: Lithium disilicate crowns can be manufactured by computer-aided design and computer-aided manufacturing (CAD-CAM) or with the heat-pressed technique. The outcome of studies comparing the effect of the manufacturing method on the marginal adaptation of these crowns is not clear. PURPOSE: The purpose of this systematic review and meta-analysis was to investigate the effect of the CAD-CAM system and pressing technique on the marginal adaptation of lithium disilicate crowns. MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A literature research was conducted in MEDLINE via PubMed and Scopus databases, relevant journal sites, and the authors' collected references, from January 2009 to April 2019. RESULTS: The electronic and manual searches that could be read in full totaled 24 studies; of which, 9 were included in the systematic review and meta-analysis, 7 of which were in vitro and 2 in vivo. Statistical analyses were conducted by using Review Manager software program. Meta-analyses were performed with the random effects model (α=.05). In vitro studies showed no difference in the manufacturing (P>.001; 95% confidence interval -0.687 to 0.632), and no significant difference was found for in vivo studies (P=.7, 95% confidence interval 0.00 to 54.77). In the joint analysis of the in vivo and in vitro articles, there was a significant difference between the manufacturing methods (P<.001). CONCLUSIONS: Differences were detected between the marginal adaptation of lithium disilicate crowns fabricated with the CAD-CAM system and the pressing technique, but the accuracy values were clinically acceptable.

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Abstract Objective To evaluate hip and knee muscular function, knee patient-reported outcome measures and hop performance in patients with a clinical indication for combined ACL+ALL reconstruction surgery compared to patients with an isolated ACL reconstruction surgery indication (preoperative phase) and to a control group. Design Cross-sectional study. Methods The sample was composed of male individuals, aged between 18 and 59 years, divided into three groups (ACL, ACL+ALL and Control). Isokinetic dynamometry was performed for the flexor and extensor knee muscles and for the hip abductors and adductors. SLHT, COHT and the Lysholm score were performed. Pain, swelling, and thigh trophism were also measured. Results The study participants were 89 male individuals: 63 in the injury group and 26 in the control group. After applying the criteria for an ALL reconstruction indication, 33 patients were assigned to the ACL Group and 30 patients to the ACL+ALL Group. Regarding knee and hip muscle function, both groups presented worse results when compared to the control group, however, did not show significant differences compared to each other. Regarding the functional variables, the ACL+ALL group showed a significantly shorter distance achieved in the Crossover Hop Test than the other groups, as well as more pain during the tests. Conclusion Knee and hip muscular functions are impaired after an ACL injury and do not seem to be influenced or worsened in individuals with greater rotational instability with clinical indications for combined reconstruction of the anterior cruciate and the anterolateral ligaments of the knee.

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Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder that causes accelerated aging and a high risk of cardiovascular complications. However, the underlying mechanisms of cardiac complications of this syndrome are not fully understood. This study modeled HGPS using cardiomyocytes (CM) derived from induced pluripotent stem cells (iPSC) derived from a patient with HGPS and characterized the biophysical, morphological, and molecular changes found in these CM compared to CM derived from a healthy donor. Electrophysiological recordings suggest that the HGPS-CM was functional and had normal electrophysiological properties. Electron tomography showed nuclear morphology alteration, and the 3D reconstruction of electron tomography images suggests structural abnormalities in HGPS-CM mitochondria, however, there was no difference in mitochondrial content as measured by Mitotracker. Immunofluorescence indicates nuclear morphological alteration and confirms the presence of Troponin T. Telomere length was measured using qRT-PCR, and no difference was found in the CM from HGPS when compared to the control. Proteomic analysis was carried out in a high-resolution system using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). The proteomics data show distinct group separations and protein expression differences between HGPS and control-CM, highlighting changes in ribosomal, TCA cycle, and amino acid biosynthesis, among other modifications. Our findings show that iPSC-derived cardiomyocytes from a Progeria Syndrome patient have significant changes in mitochondrial morphology and protein expression, implying novel mechanisms underlying premature cardiac aging.

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Although chemical additives are able to improve the efficiency of ruminal fermentation, they can leave residues in the meat. However, a blend of secondary metabolites can improve ruminal fermentation without harming the population welfare. Five levels (0.0, 1.5, 3.0, 4.5, and 6.0 g/day) of a blend of secondary metabolites from mesquite extract in sheep feed to promote increases in the nutritional value, ruminal parameters, nitrogen (N) use efficiency, microbial protein (MP) synthesis, and blood metabolites. Ten intact male Santa Inês sheep with average body weight of 55 ± 9.81 kg were used in a 5 × 5 Latin square design, replicated twice. There was a quadratic response of the digestibility of dry matter (DM), organic matter (OM), crude protein (CP), and total digestible nutrients (TDN). Microbial protein concentrations, MP synthesis efficiency, propionic acid levels, and acetic/propionic acid ratio also showed a quadratic response. The blend promoted a quadratic effect on plasma glucose and lactate levels. On the other hand, it decreased the concentrations of ammoniacal nitrogen, plasma urea, and plasma cholesterol. It is recommended to supply a blend of secondary metabolites at 3.43 g/day.

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