Development of ZTA (80% Al2O3/20% ZrO2) pre-sintered blocks for milling in CAD/CAM systems.

The present work aims to develop a production method of pre-sintered zirconia-toughened-alumina (ZTA) composite blocks for machining in a computer-aided design and computer-aided manufacturing (CAD-CAM) system. The ZTA composite comprised of 80% Al2O3 and 20% ZrO2 was synthesized, uniaxially and isostatically pressed to generate machinable CAD-CAM blocks. Fourteen green-body blocks were prepared and pre-sintered at 1000 °C. After cooling and holder gluing, a stereolithography (STL) file was designed and uploaded to manufacture disk-shaped specimens projected to comply with ISO 6872:2015. Seventy specimens were produced through machining of the blocks, samples were sintered at 1600 °C and two-sided polished. Half of the samples were subjected to accelerated autoclave hydrothermal aging (20h at 134 °C and 2.2 bar). Immediate and aged samples were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Optical and mechanical properties were assessed by reflectance tests and by biaxial flexural strength test, Vickers indentation and fracture toughness, respectively. Samples produced by machining presented high density and smooth surfaces at SEM evaluation with few microstructural defects. XRD evaluation depicted characteristic peaks of alpha alumina and tetragonal zirconia and autoclave aging had no effect on the crystalline spectra of the composite. Optical and mechanical evaluations demonstrated a high masking ability for the composite and a characteristic strength of 464 MPa and Weibull modulus of 17, with no significant alterations after aging. The milled composite exhibited a hardness of 17.61 GPa and fracture toughness of 5.63 MPa m1/2, which remained unaltered after aging. The synthesis of ZTA blocks for CAD-CAM was successful and allowed for the milling of disk-shaped specimens using the grinding method of the CAD-CAM system. ZTA composite properties were unaffected by hydrothermal autoclave aging and present a promising alternative for the manufacture of infrastructures of fixed dental prostheses.

Effect of Water Absorption and Stacking Sequences on the Tensile Properties and Damage Mechanisms of Hybrid Polyester/Glass/Jute Composites.

The aim of this work is to analyze the effect of water absorption on the mechanical properties and damage mechanisms of polyester/glass fiber/jute fiber hybrid composites obtained using the compression molding and vacuum-assisted resin transfer molding (VARTM) techniques with different stacking sequences. For this purpose, the mechanical behavior under tensile stress of the samples was evaluated before and after hygrothermal aging at different temperatures: TA, 50 °C, and 70 °C for a period of 696 h. The damage mechanism after the mechanical tests was evaluated using SEM analysis. The results showed a tendency for the mechanical properties of the composites to decrease with exposure to an aqueous ambient, regardless of the molding technique used to conform the composites. It was also observed that the stacking sequence had no significant influence on the dry composites. However, exposure to the aqueous ambient led to a reduction in mechanical properties, both for the molding technique and the stacking sequence. Damage such as delamination, fiber pull-out, fiber/matrix detachment, voids, and matrix removal were observed in the composites in the SEM analyses.

Moderating Effect of Muscular Strength in the Association between Cardiovascular Events and Depressive Symptoms in Middle-Aged and Older Adults-A Cross Sectional Study.

BACKGROUND: Depression and cardiovascular diseases are two main health conditions contributing to the global disease burden. Several studies indicate a reciprocal association between them. It is still unclear how changes in overall muscle strength may impact this association. This study aimed to analyse how muscular strength moderates the relationship between cardiovascular events and depressive symptoms among middle-aged and older adults. METHODS: Wave 8 of the population-based Survey of Health, Ageing, and Retirement in Europe (2019/2020) cross-sectional data, which included 41,666 participants (17,986 men) with a mean age of 70.65 (9.1) years old, was examined. Grip strength was measured twice on each hand using a dynamometer. The 12-item EURO-D scale was employed to gauge depressive symptoms. RESULTS: Grip strength negatively moderates the link between cardiovascular events and depressive symptoms (male: B = -0.03, 95% CI = -0.04, -0.03; female: B = -0.06, 95% CI = -0.06, -0.05). Additionally, the grip strength moderation values in the significant zone for males and females were less than 63.2 kg and 48.3 kg, respectively. CONCLUSIONS: Muscular strength modifies depressive symptoms and lessens their correlation with cardiovascular diseases. Muscle-strengthening activities could be incorporated into primary and secondary preventive strategies to reduce the burden of depression in people with CVD.

Toward Producing Biopolyethylene/Babassu Fiber Biocomposites with Improved Mechanical and Thermomechanical Properties.

The development of polymeric biocomposites containing natural fibers has grown over the years due to the properties achieved and its eco-friendly nature. Thus, biocomposites involving a polymer from a renewable source (Biopolyethylene (BioPE)) and babassu fibers (BFs), compatibilized with polyethylene grafted with maleic anhydride (MA) and acrylic acid (AA) (PE-g-MA and PE-g-AA, respectively) were obtained using melt mixing and injection molded into tensile, impact, and HDT specimens. Babassu fiber was characterized with Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TGA), and scanning electron microscopy (SEM). The biocomposites were characterized using torque rheometry, TGA, tensile strength, impact strength, thermomechanical properties, Shore D hardness, and SEM. The data indicate that the torque during the processing of compatibilized biocomposites was higher than that of BioPE/BF biocomposites, which was taken as an indication of a possible reaction between the functional groups. Compatibilization led to a substantial improvement in the elastic modulus, tensile strength, HDT, and VST and a decrease in Shore D hardness. These results were justified with SEM micrographs, which showed babassu fibers better adhered to the surface of the biopolyethylene matrix, as well as an encapsulation of these fibers. The system investigated is environmentally sustainable, and the results are promising for the technology of polymeric composites.

Induced degeneration and regeneration in aged muscle reduce tubular aggregates but not muscle function.

Introduction: Tubular aggregates (TA) are skeletal muscle structures that arise from the progressive accumulation of sarcoplasmic reticulum proteins. Cytoplasmic aggregates in muscle fibers have already been observed in mice and humans, mainly during aging and muscle disease processes. However, the effects of muscle regeneration on TA formation have not yet been reported. This study aimed to investigate the relationship between degeneration/regeneration and TA in aged murine models. We investigated the presence and quantity of TA in old males from two murine models with intense muscle degeneration and regeneration. Methods: One murine lineage was a Dmdmdx model of Duchenne muscular dystrophy (n = 6). In the other model, muscle damage was induced by electroporation in C57BL/6J wild-type mice, and analyzed after 5, 15, and 30 days post-electroporation (dpe; n = 15). Regeneration was evaluated based on the quantity of developmental myosin heavy chain (dMyHC)-positive fibers. Results: The frequency of fibers containing TA was higher in aged C57BL/6J (26 ± 8.3%) than in old dystrophic Dmdmdx mice (2.4 ± 2%). Comparing the data from induced degeneration/regeneration in normal mice revealed a reduced proportion of TA-containing fibers after 5 and 30 dpe. Normal aged muscle was able to regenerate and form dMyHC+ fibers, mainly at 5 dpe (0.1 ± 0.1 vs. 16.5 ± 2.6%). However, there was no difference in force or resistance between normal and 30 dpe animals, except for the measurements by the Actimeter device, which showed the worst parameters in the second group. Discussion: Our results suggest that TA also forms in the Dmdmdx muscle but in smaller amounts. The intense degeneration and regeneration of the old dystrophic model resulted in the generation of new muscle fibers with a lower quantity of TA. Data from electroporated wild-type mice support the idea that muscle regeneration leads to a reduction in the amount of TA. We suggest that TA accumulates in muscle fibers throughout physiological aging and that regeneration leads to the formation of new fibers without these structures. In addition, these new fibers do not confer functional benefits to the muscle.

A Comprehensive Review of Syndromic Forms of Obesity: Genetic Etiology, Clinical Features and Molecular Diagnosis.

Syndromic obesity refers to obesity occurring with additional clinical findings, such as intellectual disability/developmental delay, dysmorphic features, and congenital malformations. PURPOSE OF REVIEW: To present a narrative review regarding the genetic etiology, clinical description, and molecular diagnosis of syndromic obesity, which is a rare condition with high phenotypic variability and genetic heterogeneity. The following syndromes are presented in this review: Prader-Willi, Bardet-Biedl, Pseudohypoparathyroidism, Alström, Smith-Magenis, Cohen, Temple, 1p36 deletion, 16p11.2 microdeletion, Kleefstra, SIM1-related, Börjeson-Forssman-Lehmann, WAGRO, Carpenter, MORM, and MYT1L-related syndromes. RECENT FINDINGS: There are three main groups of mechanisms for syndromic obesity: imprinting, transcriptional activity regulation, and cellular cilia function. For molecular diagnostic, methods of genome-wide investigation should be prioritized over sequencing of panels of syndromic obesity genes. In addition, we present novel syndromic conditions that need further delineation, but evidences suggest they have a higher frequency of obesity. The etiology of syndromic obesity tends to be linked to disrupted neurodevelopment (central) and is associated with a diversity of genes and biological pathways. In the genetic investigation of individuals with syndromic obesity, the possibility that the etiology of the syndromic condition is independent of obesity should be considered. The accurate genetic diagnosis impacts medical management, treatment, and prognosis, and allows proper genetic counseling.

Germline mutations in cancer predisposition genes among pediatric patients with cancer and congenital anomalies.

BACKGROUND: Childhood cancer has a poorly known etiology, and investigating the underlying genetic background may provide novel insights. A recognized association exists between non-chromosomal birth defects and childhood cancer susceptibility. METHODS: We performed whole-exome sequencing and chromosomal microarray analysis in a cohort of childhood cancer (22 individuals, 50% with congenital anomalies) to unravel deleterious germline variants. RESULTS: A diagnostic yield of 14% was found, encompassing heterozygous variants in bona fide dominant Cancer Predisposition Genes (CPGs). Considering candidate and recessive CPGs harboring monoallelic variants, which were also deemed to play a role in the phenotype, the yield escalated to 45%. Most of the deleterious variants were mapped in genes not conventionally linked to the patient's tumor type. Relevant findings were detected in 55% of the syndromic individuals, mostly variants potentially underlying both phenotypes. CONCLUSION: We uncovered a remarkable prevalence of germline deleterious CPG variants, highlighting the significance of a comprehensive genetic analysis in pediatric cancer, especially when coupled with additional clinical signs. Moreover, our findings emphasized the potential for oligogenic inheritance, wherein multiple genes synergistically increase cancer risk. Lastly, our investigation unveiled potentially novel genotype-phenotype associations, such as SETD5 in neuroblastoma, KAT6A in gliomas, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. IMPACT: Novel gene-phenotype associations and candidate genes for pediatric cancer were unraveled, such as KAT6A in gliomas, SETD5 in neuroblastoma, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. Our analysis revealed a high frequency of deleterious germline variants, particularly in cases accompanied by additional clinical signs, highlighting the importance of a comprehensive genetic evaluation in childhood cancer. Our findings also underscored the potential for oligogenic inheritance in pediatric cancer risk. Understanding the cancer etiology is crucial for genetic counseling, often influencing therapeutic decisions and offering valuable insights into molecular targets for the development of oncological therapies.

Biodegradable PBAT/PLA blend films incorporated with turmeric and cinnamomum powder: A potential alternative for active food packaging.

Active packaging made from biodegradable polymers and natural additives appears as an ecological alternative. In addition to having antioxidant activity and enhancing food preservation, it allows mitigating the negative impacts caused by improper disposal. This study pursued to produce biodegradable films based on a polymer blend PBAT/PLA (Ecovio®) using the flat extrusion method. The films were prepared with the incorporation of 5 wt% of powdered turmeric or cinnamon as natural additives. The films obtained, and those reprocessed twice, were characterized in terms of colorimetric, UV light transmittance, water contact angle, water vapor permeability, morphology, mechanical properties, and antioxidant activity. Cinnamon reduced the UV light transmittance and made a surface more hydrophobic. Reprocessing led to greater elongation and maximum load, associated with increased dispersion and distribution, as evidenced in the morphological analysis. The films developed have significant potential for applications in active food packaging, with emphasis on cinnamon-additivated films.

Influence of abrasive dentifrices on polymeric reconstructive material properties after simulated toothbrushing.

To assess the influence of dentifrices with different abrasiveness levels on the properties of dental reconstructive materials. Forty-eight cylinders were obtained from four polymeric materials, being two CAD/CAM acrylic resins (Ivotion-Dent and Ivotion-Base), one injected acrylic resin (IvoBase-Hydrid) and one light-cured resin composite (Empress Direct). Specimens were allocated to four subgroups for toothbrushing simulation according to the dentifrice relative dentin abrasivity (RDA) and silica content: (i) RDA 0 = 0%; (ii) RDA 50 = 3%; (iii) RDA 100 = 10%; and (iv) RDA 120 = 25%. Specimens were then subjected to toothbrushing. Surface analyses [surface roughness Ra (SR) and scanning electron microscopy (SEM)] along with hardness and optical properties [translucency parameter (TP) and contrast ratio (CR)] were evaluated before and after toothbrushing. Statistical analyses were performed using ANOVA and Tukey test. A significant increase in SR was observed after toothbrushing with higher RDA toothpastes for Ivotion-Dent (100 and 120) and IvoBase-Hybrid (120). Ivotion-Base and Empress Direct presented no significant differences in SR when analyzed as a function of timepoint and RDA levels. Hardness was not influenced by toothbrushing with different RDA dentifrices, except for Empress Direct with RDA 0 toothpaste, where a decrease in the hardness was observed. TP of Ivotion-Dent and Empress Direct significantly decreased after toothbrushing with higher RDA dentifrices and CR of Ivotion-Dent, Empress Direct and IvoBase-Hybrid significantly increased with higher RDA dentifrices. The levels of dentifrice abrasiveness affected differently the SR, hardness and optical properties of polymeric reconstructive materials after toothbrushing.

Transcriptome analysis revealed immune responses in the kidney of Atlantic salmon (Salmo salar) co-infected with sea lice (Lepeophtheirus salmonis) and infectious salmon anemia virus.

Sea lice (Lepeophtheirus salmonis) and infectious salmon anemia virus (ISAv) are two of the most important pathogens in Atlantic salmon (Salmo salar) farming and typically cause substantial economic losses to the industry. However, the immune interactions between hosts and these pathogens are still unclear, especially in the scenario of co-infection. In this study, we artificially infected Atlantic salmon with sea lice and ISAv, and investigated the gene expression patterns of Atlantic salmon head kidneys in response to both lice only and co-infection with lice and ISAv by transcriptomic analysis. The challenge experiment indicated that co-infection resulted in a cumulative mortality rate of 47.8 %, while no mortality was observed in the lice alone infection. We identified 240 differentially expressed genes (DEGs) under the lice alone infection, of which 185 were down-regulated and 55 were up-regulated, while a total of 994 DEGs were identified in the co-infection, of which 206 were down-regulated and 788 were significantly up-regulated. The pathway enrichment analysis revealed that single-infection significantly suppressed the innate immune system (e.g., the complement system), whereas co-infection induced a strong immune response, leading to the activation of immune-related signaling pathways such as Toll-like receptors and NOD-like receptors pathways, as well as significant upregulation of genes related to the activation of interferon and MH class I protein complex. Our results provide the first global transcriptomic study of gene expression in the Atlantic salmon head kidney in response to co-infection with sea lice and ISAv, and provided the baseline knowledge for understanding the immune responses during co-infection.

Nutritive value of fermented soybean grains for ruminants.

Fermented soybean grain (FSBG) is considered improper to use as a protein source in animal nutrition, since it is assumed that defects cause changes on its chemical composition and favor mycotoxins production, but chemical composition data does not support this theory and in vivo studies are missing. Thus, this study aimed to evaluate the effects of FSBG in feedlot lamb diets. For that, two types of FSBG (partially fermented and completely fermented, PFSBG and CFSBG) and one standard soybean grain (SSBG) were obtained and evaluated alone or as a component of experimental diets by in vitro and in vivo studies, where FSBG totally replaced SSBG in feedlot lamb diets, which was included in the experimental diets in 17.4% on dry matter basis as protein source. Before the studies, both soybeans were sent to a specialized laboratory where no mycotoxins were detected. As a result, lower DM and carbohydrate contents but higher crude protein, fiber, and indigestible NDF contents were measured in CFSBG than in SSBG. Furthermore, both types of FSBG showed lower digestibility in vitro dry matter (IVDMD) than SSBG when evaluated separately; however, when evaluated in experimental diets, the substitution of SSBG for FSBG did not affect IVDMD. It was also observed that FSBG also had less rumen-degradable protein than SSBG (mean 47.9 vs 86.4%). In the in vivo study, FSBG did not affect nutrient intake, apparent digestibility, or animal performance (i.e., average daily gain and carcass gain). Thus, mycotoxins-free FSBG may be an alternative to totally replace SSBG in feedlot lamb diets.

Water Sorption in Hybrid Polyester/Glass/Jute Composites Processed via Compression Molding and Vacuum-Assisted Resin Transfer Molding.

The aim of this work is to analyze water sorption in hybrid polyester/glass fabric/jute fabric composites molded via compression and VARTM (Vacuum-Assisted Resin Transfer Molding). The laminates were produced with five different stacking sequences and subjected to water sorption testing at room temperature, 50 °C and 70 °C. This study consisted of two stages: experimental and theoretical stages. The composites had a fiber volume content ranging from 30% to 40%. Water absorption and diffusion coefficient in the hybrid composites were intermediate to those reinforced with a single type of fiber. There were no significant differences in these properties based on fiber arrangement once the composites reached saturation. Diffusion coefficient values were higher for specimens with jute fiber on at least one of the outer surfaces. Water sorption rates increased with higher immersion temperatures. The water sorption at saturation point was not affected by the manufacturing process. Among the hybrid composites, those with jute on the surfaces showed the highest diffusion coefficient, while those with glass on the surface had the lowest values. Higher diffusion coefficient values were observed at temperatures of 50 °C and 70 °C. The main influencing factors on the absorbed moisture content for composites are the presence and content of jute fibers in the system and the immersion temperature. The manufacturing process does not affect the water sorption at saturation point.

Alumina-toughened zirconia nanocomposite: Aging effect on microstructural, optical, and mechanical properties.

OBJECTIVES: To process an alumina-toughened zirconia (ATZ) nanocomposite and to characterize its crystalline phases, microstructure, residual stress, mechanical and optical properties before and after two different artificial aging methodologies. METHODS: Disc-shaped specimens were obtained through uniaxial pressing of a commercial ATZ powder comprised of 80%ZrO2 / 20%Al2O3, with a particle size of 50 nm and 150 nm, respectively. Sintering was performed at 1500ºC for 2 h. Groups were established according to the aging protocol as immediate (ATZ-I) and aged either in autoclave (ATZ-A) or hydrothermal reactor (ATZ-R) at 134 ºC for 20 h at 2.2 bar. Crystalline phases and microstructure were assessed by X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. Residual stress was evaluated by Raman spectroscopy. Contrast Ratio (CR) and Translucency Parameter (TP) were calculated to characterize optical properties. Mechanical properties were analyzed through Vickers microhardness, fracture toughness, and biaxial flexural strength test. RESULTS: XRD spectra of both aging protocols revealed the presence of monoclinic zirconia (20-31%), where higher phase transformation was observed after aging in hydrothermal reactor. Optical properties evaluation demonstrated high opacity (CR: 0.99) and masking ability (TP: 0.26), with no significant differences after aging. Raman spectroscopy evidenced the presence of residual compressive stresses in the aged groups, being significantly higher for ATZ-R (-215.2 MPa). As-sintered specimens revealed hardness of ∼12.3 GPa and fracture toughness of ∼1.9 MPa.m1/2. Characteristic strength was 740 MPa for ATZ-I, 804 MPa for ATZ-A, and 879 MPa for ATZ-R, with significant differences between groups. Weibull modulus ranged from 16.5 to 18.8. All groups demonstrated high reliability up to 500 MPa stress missions (99-100%), with no significant differences after aging. SIGNIFICANCE: The experimental ATZ nanocomposite presented high opacity and a high Weibull modulus. While aging created internal compressive stress responsible for an increase in characteristic strength, the nanocomposite was susceptible to hydrothermal degradation. Further studies are required to evaluate its degradation kinetics at low temperatures.

Reliability and Failure Mode of Ti-Base Abutments Supported by Narrow/Wide Implant Systems.

To assess the reliability and failure modes of Ti-base abutments supported by narrow and wide-diameter implant systems. Narrow (Ø3.5 × 10 mm) and wide (Ø5 × 10 mm) implant systems of two different manufacturers with internal conical connections (16°) and their respective Ti-base abutments (3.5 and 4.5 mm) were evaluated. Ti-base abutments were torqued to the implants, standardized metallic maxillary incisor crowns were cemented, and step stress accelerated life testing of eighteen assemblies per group was performed in three loading profiles: mild, moderate, and aggressive until fracture or suspension. Reliability for missions of 100,000 cycles at 100 and 150 N was calculated, and fractographic analysis was performed. For missions at 100 N for 100,000 cycles, both narrow and wide implant systems exhibited a high probability of survival (≥99%, CI: 94-100%) without significant differences. At 150 N, wide-diameter implants presented higher reliability (≥99%, CI: 99-100%) compared to narrow implants (86%, CI: 61-95%), with no significant differences among manufacturers. Failure mode predominantly involved Ti-base abutment fractures at the abutment platform. Ti-base abutments supported by narrow and wide implant systems presented high reliability for physiologic masticatory forces, whereas for high load-bearing applications, wide-diameter implants presented increased reliability. Failures were confined to abutment fractures.

Microbiological analysis of bacterial sealing of internal conical implants with different taper angles.

The present study evaluated the effect of the taper angle of different internal conical connection implants and cyclic loading on the implant-abutment bacterial seal. A total of 96 implant-abutment sets were divided into eight groups. Four groups of different taper degrees with cyclic mechanical loading of 500,000 cycles per sample, with a 120-N load at 2 Hz before analysis [16DC (16-degree, cycled), 11.5DC (11.5-degree, cycled), 3DC (3- degree, cycled) and 4DC (4- degree, cycled)] were compared to four control groups without cyclic loading [16D (16-degree), 11.5D (11.5-degree), 3D (3-degree), and 4D (4-degree)]. Microbiological analysis was performed by immersing all samples in a suspension containing Escherichia coli and incubating them at 37°C. After 14 days, the presence of bacterial seals was evaluated. Fisher-Freeman-Halton exact tests and binomial tests were performed (5% significance level). The groups showed significant differences in bacterial seal, and mechanical load cycling improved the bacterial seal in the 3DC group. In all other groups, no significant differences in bacterial seal were found between cycled and uncycled samples. To conclude, the internal conical connection with a 3-degree taper angle showed better results than the other connection with different angles when subjected to load cycling. However, none of the angles tested were fully effective in sealing the implant-abutment interface.

Single geometry abutment for narrow and extra-narrow implant systems: Survival and failure modes.

The use of identical prosthetic components for all implant diameters could reduce the production costs by companies and the complexity of component selection for the clinician and his team. However, it would imply in reduction of thickness of the cervical walls of tapered internal connection implants, which could compromise the reliability of narrow and extra-narrow implants. Therefore, this study aims to evaluate the probability of survival and failure modes of extra-narrow implant systems with the same internal diameter as standard-diameter implants using the same prosthetic components. It was used eigth different implant system configurations, including narrow (Ø 3.3 mm) (N) extra-narrow (Ø 2.9 mm) (EN) and extra-narrow-scalloped (Ø 2.9 mm) (ENS) implants, both with cementable abutments (Ce) or titanium bases (Tib) and one-piece implants (Ø 2.5 mm and Ø 3.0 mm) (OP) (Medens, Itu, SP, Brazil), comprising the following groups: OP 3.0; OP 2.5; N Ce; N Tib; EN Ce, EN Tib, ENS-Ce and ENS-Tib. The implants were embedded using polymethylmethacrylate acrylic resin in a 15 mm matrix. Standardized maxillary central incisor crowns were virtually designed and milled to fit on the different studied abutments and cemented using a dual self-adhesive resin cement. The specimens were submitted to SSALT (Step Stress Accelerated Life Testing) at 15 Hz in water until failure or suspension of the test, until a maximum load of 500 N. Fractographic analysis of the failed specimens were realized in scanning electron microscopy. All implant systems demonstrated high probability of survival (90-100%) for missions at 50 and 100 N and values of characteristic strength superior to 139 N. Failure modes were restricted to the abutment in all the implant configurations tested. Therefore, the use extra-narrow implants with standardized prosthetic components for different implant diameters is a viable option for the replacement of anterior teeth.

Lysolecithin-derived feed additive improves feedlot performance, carcass characteristics, and muscle fatty acid profile of Bos indicus-influenced cattle fed in a tropical environment.

Lysolecithin might increase ruminal and intestinal emulsification, leading to increased digestibility, but there is minimum information about which is the most appropriate phase to start supplementation and its impacts on feedlot performance and muscle fatty acid profile. Two experiments were conducted to evaluate the effects of phase-feeding of Lysoforte™ eXtend (LYSO). In the first experiment, 1,760 predominantly Bos indicus bullocks (initial body weight of 400 ± 0.561 kg) were allocated in a complete randomized block design. LYSO was supplemented at 1 g/1% of ether extract from the diet. Treatments were no LYSO supplementation (NON); LYSO starting during the growing period and continuing during the finishing period; LYSO starting during the finishing period (FIN); and LYSO during adaptation, growing, and finishing periods (ALL). In the second experiment, the same treatments were evaluated with 96 bullocks (64 Nellore and 32½ Nellore × ½ Angus) in a 4 × 2 factorial arrangement (treatments × genotype). For both studies, intake and average daily gain were accessed; carcass characteristics were evaluated in the first experiment, while digestibility of nutrients and profile of muscle fatty acids were measured in the second experiment. In the first experiment, LYSO increased final body weight (P < 0.022) and average daily gain (GRO and FIN; P < 0.05). In the second study, a treatment × breed × feeding phase interaction was observed with Nellore having a greater average daily gain (P < 0.05) than crossbreds in every feeding phase that LYSO was introduced to the diet. A treatment × feeding phase interaction was observed for digestibility, such that LYSO increased total dry matter (P = 0.004), crude protein (P = 0.043), and NDF (P = 0.001) digestibility during the finishing period. A treatment × breed × day classification was observed (P < 0.05). During the finishing phase, crossbreds treated with LYSO had greater DMI (P < 0.05) on very hot days than NON. Also, animals treated with LYSO presented a greater C18:3 n3 concentration (P = 0.047) in the longissimus. Overall, feeding LYSO during GRO and FIN enhanced feedlot performance and should lead to higher intakes during very hot days of the finishing feeding period.

Establishment of iPSC lines and zebrafish with loss-of-function AHDC1 variants: Models for Xia-Gibbs syndrome.

Xia-Gibbs syndrome (XGS) is a syndromic form of intellectual disability caused by heterozygous AHDC1 variants, but the pathophysiological mechanisms underlying this syndrome are still unclear. In this manuscript, we describe the development of two different functional models: three induced pluripotent stem cell (iPSC) lines with different loss-of-function (LoF) AHDC1 variants, derived by reprogramming peripheral blood mononuclear cells from XGS patients, and a zebrafish strain with a LoF variant in the ortholog gene (ahdc1) obtained through CRISPR/Cas9-mediated editing. The three iPSC lines showed expression of pluripotency factors (SOX2, SSEA-4, OCT3/4, and NANOG). To verify the capacity of iPSC to differentiate into the three germ layers, we obtained embryoid bodies (EBs), induced their differentiation, and confirmed the mRNA expression of ectodermal, mesodermal, and endodermal markers using the TaqMan hPSC Scorecard. The iPSC lines were also approved for the following quality tests: chromosomal microarray analysis (CMA), mycoplasma testing, and short tandem repeat (STR) DNA profiling. The zebrafish model has an insertion of four base pairs in the ahdc1 gene, is fertile, and breeding between heterozygous and wild-type (WT) animals generated offspring in a genotypic proportion in agreement with Mendelian law. The established iPSC and zebrafish lines were deposited on the hpscreg.eu and zfin.org platforms, respectively. These biological models are the first for XGS and will be used in future studies that investigate the pathophysiology of this syndrome, unraveling its underlying molecular mechanisms.

Skewed X-chromosome Inactivation in Women with Idiopathic Intellectual Disability is Indicative of Pathogenic Variants.

Intellectual disability (ID) is an early onset impairment in cognitive functioning and adaptive behavior, affecting approximately 1% of the population worldwide. Extreme skewing of X-chromosome inactivation (XCI) can be associated with ID phenotypes caused by pathogenic variants in the X chromosome. We analyzed the XCI pattern in blood samples of 194 women with idiopathic ID, using the androgen receptor gene (AR) methylation assay. Among the 136 patients who were informative, 11 (8%) presented with extreme or total XCI skewing (≥ 90%), which was significantly higher than expected by chance. Whole-exome data obtained from these 11 patients revealed the presence of dominant pathogenic variants in eight of them, all sporadic cases, resulting in a molecular diagnostic rate of 73% (8/11 patients). All variants were mapped to ID-related genes with dominant phenotypes: four variants in the X-linked genes DDX3X (an XCI escape gene; two cases), WDR45, and PDHA1, and four variants in the autosomal genes KCNB1, CTNNB1, YY1, and ANKRD11. Three of the autosomal genes had no obvious correlation with the observed XCI skewing. However, YY1 is a known transcriptional repressor that acts in the binding of the XIST long noncoding RNA on the inactive X chromosome, providing a mechanistic link between the pathogenic variant and the detected skewed XCI in the carrier. These data confirm that extreme XCI skewing in females with ID is highly indicative of causative X-linked pathogenic variants, and point to the possibility of identifying causative variants in autosomal genes with a XCI role.

SCAF4-related syndromic intellectual disability.

The causal link between variants in the SCAF4 gene and a syndromic form of intellectual disability (ID) was established in 2020 by Fliedner et al. Since then, no additional cases have been reported. We performed exome sequencing in a 16-year-old Brazilian male presenting with ID, epilepsy, behavioral problems, speech impairment, facial dysmorphisms, heart malformations, and obesity. A de novo pathogenic variant [SCAF4(NM_020706.2):c.374_375dup(p.Glu126LeufsTer20)] was identified. This is the second study reporting the involvement of SCAF4 in syndromic ID, and the description of the patient's clinical features contributes to defining the phenotypic spectrum of this recently described Mendelian disorder.