scholarly journals New Trends In Treacher Collins Syndrome: Bony Reconstruction And Regenerative Therapy

2021 ◽  
pp. 22
Author(s):  
◽  
Keyword(s):  
Soft Tissue ◽  
De Novo ◽  
Treatment Strategies ◽  
Fat Grafting ◽  
Treacher Collins Syndrome ◽  
Comparative Genomic ◽  
Soft Tissue Reconstruction ◽  
De Novo Mutations ◽  
Differentiation Potential ◽  
Characteristic Appearance

Aim:Treacher Collins syndrome is a rare congenital disorder of craniofacial development with a highly variable pheonotype. This syndrome occurs with an incidence of 1:50,000, and more than 60% of the cases have no previous family history and arise as the result of de novo mutations. The disorder displays an intricate underlying dysmorphology. Affected patients may suffer life-threatening airway complications and functional difficulties involving sight, hearing, speech, and feeding. Deformation of facial structures produces a characteristic appearance that includes malar-zygomatic hypoplasia, periorbital soft tissue anomalies, maxillomandibular hypoplasia, and ear anomalies. Management requires a specialized craniofacial team, as comprehensive care starts at birth and may require life-long follow-up. Standard craniofacial procedures for bony and soft tissue reconstruction are used. This article outlines current treatment strategies and future concepts for surgical and regenerative management. Methods:The new field of regenerative medicine and therapy offers the promise to improve some of these treatments. In particular, Structural Fat Grafting (lipostructure) seems to be a good strategy to restore the normal volume and contour of the face, and to provide a source of adipose-derived stem cells (ADSCs) with a multilineage differentiation potential. In this work, we present the case of a young girl with Treacher Collins Syndrome who underwent serial sessions of fat grafting in addition to other surgical bony reconstructive techniques. ADSCs have been isolated from the patient’s lipoaspirate, and compared for their stemness properties with those of a healthy subject. Conclusion:Screening of the genome of the Treacher Collins patient using array-Comparative Genomic Hybridization (array-CGH) allowed us to identify some chromosomal imbalances that are probably associated with the syndrome.Correction of these imbalances and asymmetries by modulating ADSCs could be an innovative approach to improve and stabilize the results of the surgical treatment of Treacher Collin Syndrome.

Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction

2019 ◽  
Vol 11 (490) ◽  
pp. eaau6210 ◽  
Author(s):  
Xiaowei Li ◽  
Brian Cho ◽  
Russell Martin ◽  
Michelle Seu ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Donor Site ◽  
Rabbit Model ◽  
Soft Tissue Defect ◽  
Fat Grafting ◽  
Foreign Body Response ◽  
Soft Tissue Reconstruction ◽  
Hydrogel Composite ◽  
Tissue Flaps ◽  
Tissue Restoration

Soft tissue losses from tumor removal, trauma, aging, and congenital malformation affect millions of people each year. Existing options for soft tissue restoration have several drawbacks: Surgical options such as the use of autologous tissue flaps lead to donor site defects, prosthetic implants are prone to foreign body response leading to fibrosis, and fat grafting and dermal fillers are limited to small-volume defects and only provide transient volume restoration. In addition, large-volume fat grafting and other tissue-engineering attempts are hampered by poor vascular ingrowth. Currently, there are no off-the-shelf materials that can fill the volume lost in soft tissue defects while promoting early angiogenesis. Here, we report a nanofiber-hydrogel composite that addresses these issues. By incorporating interfacial bonding between electrospun poly(ε-caprolactone) fibers and a hyaluronic acid hydrogel network, we generated a composite that mimics the microarchitecture and mechanical properties of soft tissue extracellular matrix. Upon subcutaneous injection in a rat model, this composite permitted infiltration of host macrophages and conditioned them into the pro-regenerative phenotype. By secreting pro-angiogenic cytokines and growth factors, these polarized macrophages enabled gradual remodeling and replacement of the composite with vascularized soft tissue. Such host cell infiltration and angiogenesis were also observed in a rabbit model for repairing a soft tissue defect filled with the composite. This injectable nanofiber-hydrogel composite augments native tissue regenerative responses, thus enabling durable soft tissue restoration outcomes.

Endophenotypes

2020 ◽  
pp. 184-192
Author(s):  
David Braff
Keyword(s):  
De Novo ◽  
Statistical Significance ◽  
Treatment Strategies ◽  
De Novo Mutations ◽  
Treatment Development ◽  
Cognitive Domains ◽  
Gene Transcripts ◽  
Key Issues ◽  
New Treatment ◽  
Control Designs

Since Gottesman introduced the concept of endophenotypes in schizophrenia research, the endophenotype strategy for understanding the genetics of schizophrenia has been used widely. Endophenotypes are wide-ranging laboratory-based quantitative measures from gene transcripts to neurocognition that show deficits in schizophrenia patients and their first-degree relatives. In addition, these deficits are primarily state related and cosegregate with the disorder. Quantitative endophenotypes, such as working memory, share many genes with schizophrenia itself but have 100 times the efficiency and require about 10 times fewer subjects than case-control designs to reach statistical significance for gene finding. Endophenotypes are also platforms for collaborations with scientists studying key issues including de novo mutations and methylation events in psychosis. In addition, the endophenotypes most commonly used in psychosis research are neurocognitive and tap into cognitive domains that have been identified by the FDA and MATRICS project as targets for new treatment development. Thus, the endophenotype strategy is an exciting and dynamic path for gene discovery and personalized treatment strategies in the future.

scholarly journals Free adipose tissue (FAT) graft pooling for severe dead space management

2020 ◽  
Vol 14 (3) ◽  
pp. 293-296
Author(s):  
Gustavo Souza ◽  
Robinson Pires ◽  
Egídio Santana Junior ◽  
Lydia Ferreira ◽  
Richard Yoon ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Free Flaps ◽  
Fat Grafting ◽  
Fat Graft ◽  
Soft Tissue Reconstruction ◽  
Salvage Procedure ◽  
Level Of Evidence ◽  
Space Management ◽  
Extremity Trauma ◽  
Tissue Reconstruction

Complex lower extremity trauma with large soft tissue defects requires early wound coverage to reduce the risk of complications. In particular circumstances, however, local or free flaps may be contraindicated due to local or systemic issues. This study presents a helpful and effective salvage procedure for soft tissue reconstruction that uses autologous fat grafting combined with negative pressure wound therapy. Level of Evidence V; Therapeutic Studies; Expert Opinion.

scholarly journals Experimental In-Vivo Models Used in Fat Grafting Research for Volume Augmentation in Soft Tissue Reconstruction

2017 ◽  
Vol 44 (5) ◽  
pp. 361-369 ◽  
Author(s):  
Jorge Lujan-Hernandez ◽  
Raghu Appasani ◽  
Kylee Sullivan ◽  
Leah Siegel-Reamer ◽  
Janice F. Lalikos
Keyword(s):  
Soft Tissue ◽  
Fat Grafting ◽  
Soft Tissue Reconstruction ◽  
In Vivo Models ◽  
Tissue Reconstruction

scholarly journals Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guanting Lu ◽  
Qiongling Peng ◽  
Lianying Wu ◽  
Jian Zhang ◽  
Liya Ma
Keyword(s):  
Intellectual Disability ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Array Cgh ◽  
De Novo ◽  
Current Knowledge ◽  
Comparative Genomic ◽  
De Novo Mutations ◽  
Single Nucleotide Variants ◽  
Whole Exome

Abstract Background Coffin–Siris syndrome (CSS) is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hirsutism, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. CSS represents a small group of intellectual disability, and could be caused by at least twelve genes. The genetic background is quite heterogenous, making it difficult for clinicians and genetic consultors to pinpoint the exact disease types. Methods Array-Comparative Genomic Hybridization (array-CGH) and whole exome sequencing (WES) were applied for three trios affected with intellectual disability and clinical features similar with those of Coffin–Siris syndrome. Sanger sequencing was used to verify the detected single-nucleotide variants (SNVs). Results All of the three cases were female with normal karyotypes of 46, XX, born of healthy, non-consanguineous parents. A 6q25 microdeletion (arr[hg19]6q25.3(155,966,487–158,803,979) × 1) (2.84 Mb) (case 1) and two loss-of-function (LoF) mutations of ARID1B [c.2332 + 1G > A in case 2 and c.4741C > T (p.Q1581X) in case 3] were identified. All of the three pathogenic abnormalities were de novo, not inherited from their parents. After comparison of publicly available microdeletions containing ARID1B, four types of microdeletions leading to insufficient production of ARID1B were identified, namely deletions covering the whole region of ARID1B, deletions covering the promoter region, deletions covering the termination region or deletions covering enhancer regions. Conclusion Here we identified de novo ARID1B mutations in three Chinese trios. Four types of microdeletions covering ARID1B were identified. This study broadens current knowledge of ARID1B mutations for clinicians and genetic consultors.

scholarly journals Genetic determinants of antibiotic resistance and the evolution of trade-offs during adaptation in a single patient

2021 ◽  
Author(s):  
Robert J Woods ◽  
Camilo Barbosa ◽  
Laura Koepping ◽  
Juan A. Raygoza Garay ◽  
Michael Mwangi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
De Novo ◽  
Laboratory Data ◽  
Genetic Material ◽  
Treatment Strategies ◽  
Single Patient ◽  
De Novo Mutations ◽  
Collateral Sensitivity ◽  
Trade Offs ◽  
Evolutionary Trajectories

The processes by which pathogens evolve within single hosts dictate the efficacy of treatment strategies designed to slow antibiotic resistance evolution and influence the population-wide resistance levels. The aim of this study is to describe the underlying genetic and phenotypic changes leading to antibiotic resistance within a single patient who died as resistance evolved to available antibiotics. We assess whether robust patterns of collateral sensitivity and response to combinations exist that might have been leveraged to improve therapy. Whole-genome sequencing was completed for nine isolates taken from this patient over 279 days of chronic infection with Enterobacter hormaechei, along with systematic measurements of changes in resistance against five of the most relevant drugs considered for treatment. The entirety of the genetic change is consistent with de novo mutations and plasmid loss events, without the acquisition of foreign genetic material via horizontal gene transfer. The isolates formed three genetically distinct lineages, with early evolutionary trajectories being supplanted by previously unobserved multi-step evolutionary trajectories. Importantly, no single isolate evolved resistance to all of the antibiotics considered for treatment against E. hormaechei (i.e., none was pan-resistant). Patterns of collateral sensitivity and response to combination therapy revealed contrasting patterns across this diversifying population. Translating antibiotic resistance management strategies from theoretical and laboratory data to clinical situations, such as this, may require managing diverse populations with unpredictable resistance trajectories.

scholarly journals An immunologically active, adipose-derived extracellular matrix biomaterial for soft tissue reconstruction: concept to clinical trial

2020 ◽  
Author(s):  
Amy E. Anderson ◽  
Iwen Wu ◽  
Alexis J. Parrillo ◽  
David R. Maestas ◽  
Ian Graham ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Soft Tissue ◽  
Human Subjects ◽  
Donor Site ◽  
Tissue Remodeling ◽  
Fat Grafting ◽  
Interleukin 4 ◽  
Fat Graft ◽  
Soft Tissue Reconstruction ◽  
Tissue Reconstruction

ABSTRACTSoft tissue reconstruction remains an intractable clinical challenge as current surgical options and synthetic implants may produce inadequate outcomes. Soft tissue deficits may be surgically reconstructed using autologous adipose tissue, but these procedures can lead to donor site morbidity, require multiple trips to the operating room, and have highly variable outcomes. To address the clinical need for soft tissue reconstruction, we developed an “off-the-shelf” adipose matrix from allograft human adipose tissue (acellular adipose tissue, AAT). We applied physical and chemical processing methods to remove lipids and create an injectable matrix that mimicked the properties of fat grafting materials. Biological activity was assessed using cell migration and stem cell adipogenesis assays. Characterization of the regenerative immunology properties in a murine muscle injury model revealed allograft and xenograft AAT induced pro-regenerative CD4+ T cells and macrophages with xenograft AAT attracting additional eosinophils secreting interleukin 4 (Il4). In immunocompromised mice, AAT injections retained similar tissue volumes as human fat grafts but did not have the cysts and calcifications that formed in the human fat graft implants. Combination of AAT with human adipose-derived stem cells (ASCs) resulted in lower implant volumes. However, tissue remodeling and new adipose development increased significantly with the addition of cells. Larger injected volumes of porcine-derived AAT demonstrated biocompatibility and greater volume retention when applied allogeneicly in Yorkshire cross pigs. Under a biologic IND application, AAT was implanted in healthy volunteers in abdominal tissue that was later removed (panniculectomy or abdominoplasty). The AAT implants were well tolerated and biocompatible in all eight human subjects. Analysis of implants removed between 1 and 18 weeks demonstrated increasing cellular infiltration and immune populations, suggesting continued tissue remodeling and the potential for long term tissue replacement.SUMMARYAn adipose-derived injectable biomaterial provides volume correction for soft tissue defects while promoting pro-healing immune responses.

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