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Context: The development of porous devices using materials modified with various natural agents has become a priority for bone healing processes in the oral and maxillofacial field. There must be a balance between the proliferation of eukaryotic and the inhibition of prokaryotic cells to achieve proper bone health. Infections might inhibit the formation of new alveolar bone during bone graft augmentation. Objective: This study aimed to evaluate the in vitro osteogenic behavior of human bone marrow stem cells and assess the antimicrobial response to 3D-printed porous scaffolds using propolis-modified wollastonite. Methodology: A fractional factorial design of experiments was used to obtain a 3D printing paste for developing scaffolds with a triply periodic minimal surface (TPMS) gyroid geometry based on wollastonite and modified with an ethanolic propolis extract. The antioxidant activity of the extracts was characterized using free radical scavenging methods (DPPH and ABTS). Cell proliferation and osteogenic potential using Human Bone Marrow Stem Cells (bmMSCs) were assessed at different culture time points up to 28 days. MIC and inhibition zones were studied from single strain cultures, and biofilm formation was evaluated on the scaffolds under co-culture conditions. The mechanical strength of the scaffolds was evaluated. Results: Through statistical design of experiments, a paste suitable for printing scaffolds with the desired geometry was obtained. Propolis extracts modifying the TPMS gyroid scaffolds showed favorable cell proliferation and metabolic activity with osteogenic potential after 21 days. Additionally, propolis exhibited antioxidant activity, which may be related to the antimicrobial effectiveness of the scaffolds against S. aureus and S. epidermidis cultures. The mechanical properties of the scaffolds were not affected by propolis impregnation. Conclusion: These results demonstrate that propolis-impregnated porous wollastonite scaffolds might have the potential to stimulate bone repair in maxillofacial tissue engineering applications.

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Biocompatible ceramic scaffolds offer a promising approach to address the challenges in bone reconstruction. Wollastonite, well-known for its exceptional biocompatibility, has attracted significant attention in orthopedics and craniofacial fields. However, the antimicrobial properties of wollastonite have contradictory findings, necessitating further research to enhance its antibacterial characteristics. This study aimed to explore a new approach to improve in vitro biological response in terms of antimicrobial activity and cell proliferation by taking advantage of additive manufacturing for the development of scaffolds with complex geometries by 3D printing using propolis-modified wollastonite. The scaffolds were designed with a TPMS (Triply Periodic Minimal Surface) gyroid geometric shape and 3D printed prior to impregnation with propolis extract. The paste formulation was characterized by rheometric measurements, and the presence of propolis was confirmed by FTIR spectroscopy. The scaffolds were comprehensively assessed for their mechanical strength. The biological characterization involved evaluating the antimicrobial effects against Staphylococcus aureus and Staphylococcus epidermidis, employing Minimum Inhibitory Concentration (MIC), Zone of Inhibition (ZOI), and biofilm formation assays. Additionally, SaOs-2 cultures were used to study cell proliferation (Alamar blue assay), and potential osteogenic was tested (von Kossa, Alizarin Red, and ALP stainings) at different time points. Propolis impregnation did not compromise the mechanical properties of the scaffolds, which exhibited values comparable to human trabecular bone. Propolis incorporation conferred antibacterial activity against both Staphylococcus aureus and Staphylococcus epidermidis. The implementation of TPMS gyroid geometry in the scaffold design demonstrated favorable cell proliferation with increased metabolic activity and osteogenic potential after 21 days of cell cultures.

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Alleles in the VKORC1, CYP2C9, and CYP4F2 genes can influence Warfarin dose requirement. We aimed to determine the frequency of the polymorphisms in these genes in healthy individuals from Cali, Colombia. Observational study where total blood was collected from 107 healthy donors who attended a higher educational institution in Cali, Colombia. Sanger sequencing of exons 2, 3, 5, and 7 of the CYP2C9 gene; the common promoter region of CYP (rs12777823); exon 11 of CPY4F2 and the polymorphism c.-1639G > A in the VKORC1 gene promoter was performed. CYP2C9*2, CYP2C9*3, CYP2C9*8, CYP2C9*9, CYP2C9*11, CYP4F2*3, rs12777823, and VKORC1*2 were detected. The latter had the highest frequency with 80 (74.8%) participants in a heterozygous or homozygous state. The least frequent allele was CYP2C9*11 with only 1 carrier. Combined haplotypes (VKORC1 *1/*2 or *2/*2 and CYP2C9 *1/*2 or *2/*2) were identified in 14 (13.7%) subjects. Both frequencies found in the VKORC1 and CYP2C9 alleles were similar to the ones reported for Latin Americans of European and Native American Ancestry. VKORC1*2 allele, the main genetic contributor to Warfarin dosing requirement, was the variant with the highest frequency (74.8% subjects, with a frequency of the alternative allele (A) of 50%). Our findings provide researchers with a greater insight regarding the frequency of common polymorphisms that affect anticoagulation treatment in the Cali (Colombia) population.

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Several diseases and injuries cause irreversible damage to bone tissues, which may require partial or total regeneration or replacement. Tissue engineering suggests developing substitutes that may contribute to the repair or regeneration process by using three-dimensional lattices (scaffolds) to create functional bone tissues. Herein, scaffolds comprising polylactic acid and wollastonite particles enriched with propolis extracts from the Arauca region of Colombia were developed as gyroid triply periodic minimal surfaces using fused deposition modeling. The propolis extracts exhibited antibacterial activity against Staphylococcus aureus (ATCC 25175) and Staphylococcus epidermidis (ATCC 12228), which cause osteomyelitis. The scaffolds were characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, contact angle, swelling, and degradation. Their mechanical properties were assessed using static and dynamic tests. Cell viability/proliferation assay was conducted using hDP-MSC cultures, while their bactericidal properties against monospecies cultures (S. aureus and S. epidermidis) and cocultures were evaluated. The wollastonite particles did not affect the physical, mechanical, or thermal properties of the scaffolds. The contact angle results showed that there were no substantial differences in the hydrophobicity between scaffolds with and without particles. Scaffolds containing wollastonite particles suffered less degradation than those produced using PLA alone. A representative result of the cyclic tests at Fmax = 450 N showed that the maximum strain reached after 8000 cycles is well below the yield strain (i.e., <7.5%), thereby indicating that even under these stringent conditions, these scaffolds will be able to work properly. The scaffolds impregnated with propolis showed a lower % of cell viability using hDP-MSCs on the 3rd day, but these values increased on the 7th day. These scaffolds exhibited antibacterial activity against the monospecies cultures of S. aureus and S. epidermidis and their cocultures. The samples without propolis loads did not show inhibition halos, whereas those loaded with EEP exhibited halos of 17.42 ± 0.2 mm against S. aureus and 12.9 ± 0.5 mm against S. epidermidis. These results made the scaffolds possible bone substitutes that exert control over species with a proliferative capacity for the biofilm-formation processes required for typical severe infectious processes.

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Osteogenesis imperfecta (OI) is a group of genetic skeletal disorders, with a prevalence of 1 in 15,000-20,000 births. OI type V has been described in approximately 150 cases and all patients carry the variant (c.-14C> T) in the IFITM5 gene. However, two other variants, p.S40L and p.N48S have been reported in this gene, leading to clinical phenotypes different from OI type V. Here we described a patient with multiple bone fractures, scoliosis, skull alteration (plagiocephaly), bone deformation, bone rickets, and intramedullary epithelioid osteosarcoma that bears the recently reported heterozygous variant c.143A>G (p.N48S) in the IFITM5 gene. This case supports the pathogenicity of this new variant in the IFITM5 gene and adds information regarding its clinical phenotype.

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Mowat-Wilson syndrome is a rare, autosomal dominant neurodevelopmental disorder characterized by distinctive facial gestalt and intellectual disability that is often associated with microcephaly, seizures and multiple congenital anomalies, mainly heart defects. More than 350 patients and 180 genetic variants in the ZEB2 gene, have been reported with an estimated frequency of 1 per 70,000 births. Here we report a Colombian female patient with facial gestalt, intellectual disability, microcephaly, congenital heart defects, hypothyroidism and middle ear defect associated with the nonsense pathogenic variant c.2761C>T (p.Arg921Ter) in the ZEB2 gene. This case contributes to the understanding of the clinical complications and the natural history of this complex and clinically heterogeneous disorder but also to the awareness that patients with heart congenital defects and dysmorphic facies may present an underlying genetic disorder.

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Neurofibromatosis type 1 is one of the most common genetic autosomal dominant disorders described, with a prevalence of 1 in 2000 to 1 in 3000 individuals. It is characterized by skin, nerves, and bone abnormalities. Non-related to NF1, hypospadias is a displacement in the urethral opening which in the majority of patients has an idiopathic cause. Here, we describe a patient with neurofibromatosis type 1, hypospadias, and unilateral cryptorchidism. The heterozygous variants c.6789_6792delTTAC, p.(Tyr2264Thrfs*5) and c.140A>G, p.(Tyr47Cys) were found in the NF1 and NR5A1 genes, respectively. This case contributes to the phenotypical characterization of patients with NF1 but also with hypospadias caused by a mutation in the NR5A1 gene, which usually leads to severe sex disorders.

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BACKGROUND: 2q37 deletion syndrome is a rare autosomal dominant disorder caused by deletions in the 2q37 cytobands leading to developmental delay, intellectual disability, behavioral abnormalities and dysmorphic craniofacial features with more than 115 patients described worldwide. CASE PRESENTATION: We describe a Colombian 3-year-old patient with verbal communication delay, umbilical hernia, facial dysmorphic features, hypotonia, and macrocephaly with normal magnetic resonance imaging. Microarray-based comparative genomic hybridization revealed a 5.9 Mb deletion in the 2q37.2 and 2q37.3 regions, eliminating 60 protein-coding genes in one of her chromosomes 2 and allowing the diagnosis of 2q37 deletion syndrome in this patient. Therapeutic interventions so far were the surgical correction of the umbilical hernia. CONCLUSIONS: Genetic tests are important tools for the diagnosis of clinically complex and infrequent conditions but also for timely diagnosis that allows appropriate surveillance, interventions, and genetic counseling. This case also provides information for expanding the phenotypical and genetic characterization of 2q37 deletion syndrome.

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AIM: To evaluate and describe lymphocyte populations' and B cell subsets' frequencies in patients presenting with Predominantly antibody deficiencies (PAD) and diagnosed with bronchiectasis or recurrent pneumonia seen in Cali (Colombian Southwest region). MATERIALS AND METHODS: 16 subjects with PAD, 20 subjects with pulmonary complications (bronchiectasis or recurrent pneumonia) and 20 healthy donors (HD). Controls and probands between 14 and 64 years old, regardless of gender were included. Lymphocyte populations (T, B and NK cells) and B cell subsets were evaluated in peripheral blood mononuclear cells using flow cytometry, T/B/NK reagent and the pre-germinal center antibody panel proposed by the EUROflow consortium were used. EUROclass and the classification proposed by Driessen et al. were implemented. RESULTS: CVID patients exhibited increase absolute numbers of CD8+ T cells and reduce NK cells as compare with HD, other PAD cases or pulmonary complications. PAD B cell subsets were disturbed when compared to the age range-matched healthy donors. Among B cell subsets, the memory B cell compartment was the most affected, especially switched memory B cells. Four participants were classified as B- and two CVID as smB-Trnorm and smB-21low groups according to EUROclass classification. The most frequent patterns proposed by Driessen et al. were B cell production and germinal center defect. CONCLUSIONS: B cell subsets, especially memory B cells, are disturbed in PAD patients from Southwestern Colombia. To the best of our knowledge this is the most comprehensive study of B cell subsets in Colombian adults.

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White-Sutton syndrome is a rare type of autosomal dominant neurodevelopmental disorder caused by mutations, mostly de novo, in the POGZ gene. No more than 120 patients have been described so far in the literature. Common clinical manifestations include intellectual disability, developmental delay, autism spectrum disorder, other behavioral abnormalities, sleeping problems, hyperactivity and visual problems. We describe a 20-year-old male patient from Colombia who presented with delayed psychomotor development, intellectual disability, obesity, sleep difficulties, hypotonia, hypogonadism, gynecomastia, visual abnormalities and several facial dysmorphisms. Genetic testing showed a novel heterozygous frameshift variant (c.3308del; p.Leu1103Profs*19) in the POGZ gene (NM_015100.3). This is the first report of a diagnosed patient with WHSUS in Colombia.