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1.
mSystems ; 9(2): e0088723, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38259105

RESUMO

Disturbance events can impact ecological community dynamics. Understanding how communities respond to disturbances and how those responses can vary is a challenge in microbial ecology. In this study, we grew a previously enriched specialized microbial community on either cellulose or glucose as a sole carbon source and subjected them to one of five different disturbance regimes of varying frequencies ranging from low to high. Using 16S rRNA gene amplicon sequencing, we show that the community structure is largely driven by substrate, but disturbance frequency affects community composition and successional dynamics. When grown on cellulose, bacteria in the genera Cellvibrio, Lacunisphaera, and Asticcacaulis are the most abundant microbes. However, Lacunisphaera is only abundant in the lower disturbance frequency treatments, while Asticcacaulis is more abundant in the highest disturbance frequency treatment. When grown on glucose, the most abundant microbes are two Pseudomonas sequence variants and a Cohnella sequence variant that is only abundant in the highest disturbance frequency treatment. Communities grown on cellulose exhibited a greater range of diversity (1.95-7.33 Hill 1 diversity) that peaks at the intermediate disturbance frequency treatment or one disturbance every 3 days. Communities grown on glucose, however, ranged from 1.63 to 5.19 Hill 1 diversity with peak diversity at the greatest disturbance frequency treatment. These results demonstrate that the dynamics of a microbial community can vary depending on substrate and the disturbance frequency and may potentially explain the variety of diversity-disturbance relationships observed in microbial systems.IMPORTANCEA generalizable diversity-disturbance relationship (DDR) of microbial communities remains a contentious topic. Various microbial systems have different DDRs. Rather than finding support or refuting specific DDRs, we investigated the underlying factors that lead to different DDRs. In this study, we measured a cellulose-enriched microbial community's response to a range of disturbance frequencies from high to low, across two different substrates: cellulose and glucose. We demonstrate that the community displays a unimodal DDR when grown on cellulose and a monotonically increasing DDR when grown on glucose. Our findings suggest that the same community can display different DDRs. These results suggest that the range of DDRs we observe across different microbial systems may be due to the nutritional resources microbial communities can access and the interactions between bacteria and their environment.


Assuntos
Microbiota , RNA Ribossômico 16S/genética , Microbiota/genética , Bactérias , Celulose , Glucose
2.
bioRxiv ; 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37662195

RESUMO

Disturbance events can impact ecological community dynamics. Understanding how communities respond to disturbances, and how those responses can vary, is a challenge in microbial ecology. In this study, we grew a previously enriched specialized microbial community on either cellulose or glucose as a sole carbon source, and subjected them to one of five different disturbance regimes of varying frequencies ranging from low to high. Using 16S rRNA gene amplicon sequencing, we show that community structure is largely driven by substrate, but disturbance frequency affects community composition and successional dynamics. When grown on cellulose, bacteria in the genera Cellvibrio, Lacunisphaera, and Asticaccacaulis are the most abundant microbes. However, Lacunisphaera is only abundant in the lower disturbance frequency treatments, while Asticaccaulis is more abundant in the highest disturbance frequency treatment. When grown on glucose, the most abundant microbes are two Pseudomonas sequence variants, and a Cohnella sequence variant that is only abundant in the highest disturbance frequency treatment. Communities grown on cellulose exhibited a greater range of diversity (0.67-1.99 Shannon diversity and 1.38-5.25 Inverse Simpson diversity) that peak at the intermediate disturbance frequency treatment, or 1 disturbance every 3 days. Communities grown on glucose, however, ranged from 0.49-1.43 Shannon diversity and 1.37- 3.52 Inverse Simpson with peak diversity at the greatest disturbance frequency treatment. These results demonstrate that the dynamics of a microbial community can vary depending on substrate and the disturbance frequency, and may potentially explain the variety of diversity-disturbance relationships observed in microbial ecosystems.

3.
Life Sci Alliance ; 6(11)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37666666

RESUMO

Ras proteins are membrane-bound GTPases that regulate essential cellular processes at the plasma membrane (PM). Constitutively active mutations of K-Ras, one of the three Ras isoforms in mammalian cells, are frequently found in human cancers. Ferrocene derivatives, which elevate cellular reactive oxygen species (ROS), have shown to block the growth of non-small cell lung cancers harboring oncogenic mutant K-Ras. Here, we tested a novel ferrocene derivative on the growth of pancreatic ductal adenocarcinoma and non-small cell lung cancer. Our compound, which elevated cellular ROS levels, inhibited the growth of K-Ras-driven cancers, and abrogated the PM binding and signaling of K-Ras in an isoform-specific manner. These effects were reversed upon antioxidant supplementation, suggesting a ROS-mediated mechanism. We further identified that K-Ras His95 residue plays an important role in this process, and it is putatively oxidized by cellular ROS. Together, our study demonstrates that the redox system directly regulates K-Ras/PM binding and signaling via oxidative modification at the His95, and proposes a role of oncogenic mutant K-Ras in the recently described antioxidant-induced growth and metastasis of K-Ras-driven cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Pancreáticas , Humanos , Animais , Antioxidantes , Metalocenos/farmacologia , Espécies Reativas de Oxigênio , Oxirredução , Estresse Oxidativo , Mamíferos
4.
Cureus ; 15(7): e41426, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37546095

RESUMO

Topically applied compounds containing camphor and menthol have been used to alleviate pain, cold symptoms, and pruritus, historically predominantly in East Asia. Being not studied well, they are less recognized in Western medicine. Given the commonality of pain, pruritus, and cold symptoms in addition to the growing need for non-opioid treatment options, the authors investigated clinical applications of such compounds for their over-counter usage. The purpose was to analyze current clinical research and applications regarding the use of these topical agents. This study involved a bibliometric analysis of peer-reviewed articles, published in English and indexed in PubMed from 2010 to 2022, pertaining to camphor- and menthol-containing compounds. There were 103 results, of which 15 (14.6%) articles were related to the treatment of disorders related to health, such as upper respiratory infection, pain, and pruritus. Excluded were "non-research" articles (e.g., letters to the editor), articles that do not involve human subjects, reports of improper application or misuse (e.g., ingestion), and articles pertaining to intraoral, intranasal, and ophthalmic agents. Of these articles, the originating journals, respective journal impact factor scores, publication years, study designs, and study topics were identified. Underlying trends and themes regarding clinically relevant research on these compounds were subsequently discerned. Based on this analysis, topical agents containing camphor and menthol are potentially effective at treating pain, upper respiratory infection symptoms, and pruritus in addition to potentially functioning as an antimicrobial. However, with a limited number of studies addressing these compounds' uses in each application, no definitive recommendation can be made regarding their use. Given the promising results of earlier studies, the authors recommend that more primary research, particularly randomized, double-blind controlled studies, be done regarding clinical applications of these substances.

5.
bioRxiv ; 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37034642

RESUMO

Ras proteins are membrane-bound GTPases that regulate essential cellular processes at the plasma membrane (PM). Constitutively active mutations of K-Ras, one of the three Ras isoforms in mammalian cells, are frequently found in human cancers. Ferrocene derivatives, which elevate cellular reactive oxygen species (ROS), have shown to block the growth of non-small cell lung cancers (NSCLCs) harboring oncogenic mutant K-Ras. Here, we developed and tested a novel ferrocene derivative on the growth of human pancreatic ductal adenocarcinoma (PDAC) and NSCLC. Our compound inhibited the growth of K-Ras-dependent PDAC and NSCLC and abrogated the PM binding and signaling of K-Ras, but not other Ras isoforms. These effects were reversed upon antioxidant supplementation, suggesting a ROS-mediated mechanism. We further identified K-Ras His95 residue in the G-domain as being involved in the ferrocene-induced K-Ras PM dissociation via oxidative modification. Together, our studies demonstrate that the redox system directly regulates K-Ras PM binding and signaling via oxidative modification at the His95, and proposes a role of oncogenic mutant K-Ras in the recently described antioxidant-induced metastasis in K-Ras-driven lung cancers.

6.
J Hand Surg Glob Online ; 5(2): 189-195, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36974302

RESUMO

Purpose: This biomechanical study evaluated the effect of intramedullary screw diameter and length relative to 3-point bending force and torsional force when used to stabilize metacarpal shaft fractures. Methods: Transverse osteotomies were made in the proximal metacarpal shaft in 36 middle finger metacarpal fourth-generation composite Sawbones. To compare screw diameters, antegrade intramedullary screws of 30-mm length were placed in 6 metacarpals, which included 4.7-mm Acutrak 2, Standard Acutrak 2 (4.0 mm), and Mini-Acutrak 2 (3.5 mm) screws. To compare screw lengths, metacarpals were fixated with Standard Acutrak 2 screws of 26, 30, or 34 mm in length, with screw tips bypassing the osteotomy by 6, 10, or 14 mm, respectively. A 6 degrees of freedom robot was used for torsional and 3-point bending testing. Results: Increasing screw diameter demonstrated significant differences in both 3-point bending and torsional strengths. Maximum torsional loads were 69 Ncm (4.7-mm Acutrak 2), 45 Ncm (Standard Acutrak 2), and 27 Ncm (Mini-Acutrak 2) (P < .05). Loads to failure in the 3-point bending tests were 916 N (4.7-mm Acutrak 2), 713 N (Standard Acutrak 2), and 284 N (Mini-Acutrak 2) (P < .05). Differing screw lengths demonstrated significant differences with maximum torsional loads when comparing the 26-mm screws (22 Ncm) with 30- and 34-mm screws (45 and 55 Ncm, respectively) (P < .05). The 3-point dorsal bending strengths were significantly different between the 26-mm screws (320 N) and 30- and 34-mm screws (713 N and 702 N, respectively) (P < .05). Conclusions: The results demonstrated significantly higher torsional strength and resistance to 3-point bending with larger intramedullary screw diameters. Further, when selecting the intramedullary screw length, the screw tip should pass at least 10 mm beyond the fracture. Clinical Relevance: This study provided biomechanical evidence to guide surgeons in selecting intramedullary screw diameter and length for treating metacarpal fractures.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36212728

RESUMO

Symphalangism is a rare, congenital syndrome involving ankylosis of the interphalangeal joints. We present a rare case of fracture at the level of a fused proximal interphalangeal joint in a patient with proximal symphalangism of the hand. Nonoperative management with splinting resulted in osseous healing and restored baseline function.

8.
Appl Environ Microbiol ; 87(14): e0017821, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33962985

RESUMO

Within animal-associated microbiomes, the functional roles of specific microbial taxa are often uncharacterized. Here, we use the fungus-growing ant system, a model for microbial symbiosis, to determine the potential defensive roles of key bacterial taxa present in the ants' fungus gardens. Fungus gardens serve as an external digestive system for the ants, with mutualistic fungi in the genus Leucoagaricus converting the plant substrate into energy for the ants. The fungus garden is host to specialized parasitic fungi in the genus Escovopsis. Here, we examine the potential role of Burkholderia spp. that occur within ant fungus gardens in inhibiting Escovopsis. We isolated members of the bacterial genera Burkholderia and Paraburkholderia from 50% of the 52 colonies sampled, indicating that members of the family Burkholderiaceae are common inhabitants in the fungus gardens of a diverse range of fungus-growing ant genera. Using antimicrobial inhibition bioassays, we found that 28 out of 32 isolates inhibited at least one Escovopsis strain with a zone of inhibition greater than 1 cm. Genomic assessment of fungus garden-associated Burkholderiaceae indicated that isolates with strong inhibition all belonged to the genus Burkholderia and contained biosynthetic gene clusters that encoded the production of two antifungals: burkholdine1213 and pyrrolnitrin. Organic extracts of cultured isolates confirmed that these compounds are responsible for antifungal activities that inhibit Escovopsis but, at equivalent concentrations, not Leucoagaricus spp. Overall, these new findings, combined with previous evidence, suggest that members of the fungus garden microbiome play an important role in maintaining the health and function of fungus-growing ant colonies. IMPORTANCE Many organisms partner with microbes to defend themselves against parasites and pathogens. Fungus-growing ants must protect Leucoagaricus spp., the fungal mutualist that provides sustenance for the ants, from a specialized fungal parasite, Escovopsis. The ants take multiple approaches, including weeding their fungus gardens to remove Escovopsis spores, as well as harboring Pseudonocardia spp., bacteria that produce antifungals that inhibit Escovopsis. In addition, a genus of bacteria commonly found in fungus gardens, Burkholderia, is known to produce secondary metabolites that inhibit Escovopsis spp. In this study, we isolated Burkholderia spp. from fungus-growing ants, assessed the isolates' ability to inhibit Escovopsis spp., and identified two compounds responsible for inhibition. Our findings suggest that Burkholderia spp. are often found in fungus gardens, adding another possible mechanism within the fungus-growing ant system to suppress the growth of the specialized parasite Escovopsis.


Assuntos
Antifúngicos/metabolismo , Formigas , Burkholderia/metabolismo , Hypocreales/crescimento & desenvolvimento , Lipopeptídeos/metabolismo , Parasitos/crescimento & desenvolvimento , Pirrolnitrina/metabolismo , Animais , Burkholderia/genética , Microbiota , Família Multigênica , Filogenia , Simbiose
9.
J Hand Surg Am ; 46(2): 149.e1-149.e8, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33092908

RESUMO

PURPOSE: This study evaluated metacarpal morphology for antegrade placement of intramedullary headless compression screws (IMHCS) for metacarpal fracture fixation. METHODS: We analyzed 100 hand computed tomography scans to quantify cortical thickness, intramedullary diameter, and metacarpal lengths. In addition, dorsal or ulnar overhang of the metacarpals over their respective carpal bones was measured. We also predicted optimal entry points for guidewire placement at the metacarpal head. RESULTS: The ring finger metacarpal had the narrowest medullary canal width (coronal, 2.8 mm; sagittal, 3.5 mm). Not counting the thumb, the little finger metacarpal had the widest midshaft medullary width of 4.1 mm in the coronal plane and the middle metacarpal was widest in the sagittal plane with canal width of 3.9 mm. On average, there was maximal dorsal overhang at the base of the middle metacarpal (4.2 mm) and maximal ulnar overhang at the base of the small metacarpal (3.9 mm). The optimal entry point for guidewire placement over each metacarpal head was approximately 3.5 to 3.8 mm volar to the dorsal cortex. CONCLUSIONS: Minimum IMHCS diameters of 3.5 mm for the ring and 4.0 mm for the index, middle and little fingers are necessary to achieve interference fit within the medullary canal. Minimum screw lengths of 38 mm would be needed to ensure 6 mm fixation past the midshaft of the metacarpals. Antegrade IMHCS for fixation of proximal metacarpal fractures may be most feasible with thumb, middle, and little finger metacarpals because there was larger dorsal or ulnar overhang to allow screw placement without violating the carpometacarpal joints. CLINICAL RELEVANCE: Our analysis provides a reference guide for intramedullary screw sizes for each metacarpal of the hand to achieve interference fit with fracture fixation. Furthermore, the dorsal and ulnar overhangs of the metacarpal bases suggest the practicality of antegrade IMHCS fixation.


Assuntos
Fraturas Ósseas , Ossos Metacarpais , Parafusos Ósseos , Fixação Interna de Fraturas , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Ossos Metacarpais/diagnóstico por imagem , Ossos Metacarpais/cirurgia , Tomografia Computadorizada por Raios X
10.
J Hand Surg Am ; 46(5): 428.e1-428.e7, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33358079

RESUMO

PURPOSE: Surgical options for displaced metacarpal shaft fractures include the use of Kirschner wires, plates and screws, and most recently, intramedullary headless compression screws (IMHCS), which have been reported using only retrograde insertion through the metacarpal head. We evaluated IMHCS fixation of metacarpal shaft fractures through an antegrade approach in a cadaver model. METHODS: We performed antegrade placement of IMHCS in 10 cadaver hands including all 5 digits (total of 50). Displaced transverse proximal metacarpal shaft fractures were created and reduced with a retrograde guidewire from the metacarpal head across the shaft fracture and exiting the metacarpal base. This was retrieved through a 6-mm dorsal wrist incision and overdrilled before the placement of a 4.1-mm-diameter IMHCS in the ring finger and a 4.7-mm screw in all other metacarpals. After IMHCS placement, carpometacarpal (CMC) joint violation was measured along with the optimal starting point for the guidewire on the metacarpal head relative to the dorsal cortex. RESULTS: In all 50 metacarpals, we achieved successful fracture reduction and fixation without violating the extensor mechanism at the wrist. Our retrograde guidewire entry point through the metacarpal head ranged from 4.2 to 4.7 mm volar to the dorsal cortex. The actual area of CMC joint violated by IMHCS placement was largest in the index CMC joint (4.9%), followed by the middle (3.7%), little (2.9%), ring (0.5%), and thumb joints (0.2%). CONCLUSIONS: Placement of IMHCS through an antegrade approach from the CMC joint can be performed effectively for all transverse metacarpal fractures, including the thumb, using a limited incision. There is minimal violation of the articular surfaces of the trapezium, capitate, and hamate for the thumb, middle, ring, and little metacarpals. CLINICAL RELEVANCE: Antegrade IMHCS fixation successfully avoids the potential morbidity of creating a metacarpal head articular surface or extensor mechanism defect at the metacarpophalangeal joint seen with the retrograde approaches.


Assuntos
Fixação Intramedular de Fraturas , Fraturas Ósseas , Ossos Metacarpais , Parafusos Ósseos , Cadáver , Fixação Interna de Fraturas , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Ossos Metacarpais/diagnóstico por imagem , Ossos Metacarpais/cirurgia
11.
Elife ; 92020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32479262

RESUMO

The Krüppel-associated box zinc finger protein (KRAB-ZFP) family diversified in mammals. The majority of human KRAB-ZFPs bind transposable elements (TEs), however, since most TEs are inactive in humans it is unclear whether KRAB-ZFPs emerged to suppress TEs. We demonstrate that many recently emerged murine KRAB-ZFPs also bind to TEs, including the active ETn, IAP, and L1 families. Using a CRISPR/Cas9-based engineering approach, we genetically deleted five large clusters of KRAB-ZFPs and demonstrate that target TEs are de-repressed, unleashing TE-encoded enhancers. Homozygous knockout mice lacking one of two KRAB-ZFP gene clusters on chromosome 2 and chromosome 4 were nonetheless viable. In pedigrees of chromosome 4 cluster KRAB-ZFP mutants, we identified numerous novel ETn insertions with a modest increase in mutants. Our data strongly support the current model that recent waves of retrotransposon activity drove the expansion of KRAB-ZFP genes in mice and that many KRAB-ZFPs play a redundant role restricting TE activity.


Assuntos
Elementos de DNA Transponíveis/genética , DNA , Proteínas Repressoras , Retroelementos/genética , Dedos de Zinco/genética , Animais , Sistemas CRISPR-Cas , DNA/química , DNA/genética , DNA/metabolismo , Evolução Molecular , Edição de Genes , Camundongos , Camundongos Knockout , Mutação/genética , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
12.
Aesthet Surg J ; 40(2): NP52-NP58, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29635460

RESUMO

Lymphomas associated with implants are predominantly of T-cell type-with anaplastic large cell lymphoma (ALCL) being most reported. That said, to date, 6 cases of B-cell lymphoma associated with breast implants have been reported. All cases exhibited unilateral breast involvement. Here, the authors report a case of low-grade B-cell lymphoma occurring bilaterally in a 34-year-old woman with a history of Poly Implant Prosthese silicone implants at age 20, T-cell angioimmunoblastic lymphoma, and subsequent myeloablative double cord blood transplantation. Lymphoma cells were positive for CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, with very low Ki-67 of 1%. Nevertheless, cases of ALCL associated with breast implants are rare but much more documented in the literature than B-cell lymphomas associated with breast implants, as in this patient. Identification of a relationship between breast cancer and silicone is still ongoing in the literature, with long-term clinical follow up required. More research will be necessary to fully characterize the occurrence, course, and association of this disease with breast implants in order to properly guide diagnosis and management.


Assuntos
Implantes de Mama/efeitos adversos , Neoplasias da Mama/etiologia , Linfoma de Células B/etiologia , Adulto , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Linfoma de Células B/diagnóstico , Géis de Silicone/efeitos adversos
13.
Plast Reconstr Surg Glob Open ; 7(5): e2263, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31333979

RESUMO

BACKGROUND: Recurrence rates following surgical intervention for Dupuytren's disease (DD) remains high. In this study, we investigate the use of acellular dermal matrix (ADM) to reduce recurrence and improve long-term clinical outcome. METHODS: We examined 132 patients undergoing open fasciectomy for DD from 2007 to 2017. The experimental group had a sheet of ADM (FlexHD) sutured into the surgical bed controls were not closed with ADM. Patient characteristics, range of motion, and complications were examined. RESULTS: Twenty-eight (21.2%) patients were treated with acellular dermal matrix, whereas 104 (78.8%) patients were not. The median age was 67.0 years (range 34-91 years). with no differences between group regarding age, comorbidities, and laterality. The mean preoperative interphalangeal joint flexion contracture in the ADM group of 66.5 ± 29.9 degrees was corrected to 9.7 ± 12.4 degrees, whereas the mean metacarpophalangeal joint preoperative flexion contracture of 51.4 ± 23.9 degrees was corrected to 7.8 ± 14.1 degrees at postoperative examination (P < 0.05). The median follow-up was 18.7 months, during which the recurrence of contracture was observed in 1 of 28 patients in the group receiving ADM compared with 9 of 104 in the control group (P = 0.37). There were no differences in the incidence of minor wound complications observed. CONCLUSION: The adjunct placement of acellular dermal matrix into the wound bed following fasciectomy for DD may be an important surgical strategy to reduce recurrence rates as well as augment coverage of exposed vital structures in cases of severe flexion contracture.

14.
Plast Reconstr Surg Glob Open ; 6(10): e1900, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30534485

RESUMO

BACKGROUND: Plastic surgery residency program websites (PSRWs) remain a major resource for applicants to one of the most competitive specialties in medicine, yet it is unclear how the website content aligns with information applicants need. OBJECTIVE: To evaluate PSRWs and whether they are meeting applicant needs. METHODS: An anonymous online survey of 2016 plastic and reconstructive surgery applicants evaluated the use of PSRWs and information desired. Two researchers then independently analyzed all 93 PSRWs in the United States to determine whether the websites met the needs of applicants based on a quantitative scoring system. RESULTS: Out of 369 total applicants to plastic surgery, the survey was sent to the 189 applicants to University of Southern California, and 87 responded (46% response rate). Ninety-eight percentage of respondents used websites during the application process. For 31%, websites served as the only source of information. Websites were moderately (60%) and only slightly useful (32%). For 22% and 34%, the quality of a website influenced their decision to apply or interview, respectively. Out of the 22 common components between the applicant survey and scoring assessment of websites, there was a significant difference in 17 components (77%) between those rated as "important" by applicants and availability of the corresponding component on websites (P < 0.05). Average (SD) score among websites was 18.7 (5.3) out of 49 maximum points (36.9%). Over 30% of websites displayed broken links or missing or outdated information. Only 19.6% displayed a link to provide website feedback. CONCLUSIONS: PSRWs commonly include pertinent information that is useful; however, most are lacking components valued by applicants. These findings can help guide the design, content, and improvement of PSRWs to be quality resources for applicants.

15.
Plast Reconstr Surg ; 141(4): 949-959, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29595730

RESUMO

BACKGROUND: In late presentation of brachial plexus trauma, it is unclear whether donor nerves should be devoted to nerve reconstruction or reserved for free functional muscle transfer. The authors systematically reviewed recovery of elbow flexion after nerve reconstruction versus free functional muscle transfer for late, traumatic brachial plexus palsy. METHODS: A systematic review was performed using the PubMed, Embase, and Cochrane databases to identify all cases of traumatic brachial plexus palsy in patients aged 18 years or older. Patients who underwent late (≥12 months) nerve reconstruction or free functional muscle transfer for elbow flexion were included. Age, time to operation, and level of brachial plexus injury were recorded. British Medical Research Council grade for strength and range of motion were evaluated for elbow flexion. RESULTS: Thirty-three studies met criteria, for a total of 103 patients (nerve reconstruction, n = 53; free functional muscle transfer, n = 50). There were no differences across groups regarding surgical age (time from injury) and preoperative elbow flexion. For upper trunk injuries, 53 percent of reconstruction patients versus 100 percent of muscle transfer patients achieved grade M3 or greater strength, and 43 percent of reconstruction patients versus 70 percent of muscle transfer patients achieved grade M4 or greater strength. Of the total brachial plexus injuries, 37 percent of reconstruction patients versus 78 percent of muscle transfer patients achieved grade M3 or greater strength, and 16 percent of reconstruction patients versus 46 percent of muscle transfer patients achieved grades M4 or greater strength. CONCLUSION: In late presentation of traumatic brachial plexus injuries, donor nerves should be reserved for free functional muscle transfer to restore elbow flexion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Neuropatias do Plexo Braquial/cirurgia , Articulação do Cotovelo/fisiologia , Retalhos de Tecido Biológico/transplante , Músculo Esquelético/transplante , Procedimentos Neurocirúrgicos/métodos , Traumatismos dos Nervos Periféricos/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Plexo Braquial/lesões , Neuropatias do Plexo Braquial/etiologia , Neuropatias do Plexo Braquial/fisiopatologia , Humanos , Traumatismos dos Nervos Periféricos/fisiopatologia , Recuperação de Função Fisiológica , Resultado do Tratamento
16.
Cell ; 173(1): 221-233.e12, 2018 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29551271

RESUMO

Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 (Igf2-P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2-P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand. These interactions arise from a shortened minor groove caused by an AT-rich stretch, suggesting adaptability of ZF arrays to sequence variations. Despite conservation in mammals, mutations at Igf2 and ZFP568 reduce their binding affinity in chimpanzee and humans. Our studies provide important insights into the evolutionary and structural dynamics of ZF-DNA interactions that play a key role in mammalian development and evolution.


Assuntos
DNA/metabolismo , Proteínas Nucleares/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Proteínas de Transporte/química , Proteínas de Transporte/classificação , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , DNA/química , Humanos , Fator de Crescimento Insulin-Like II/química , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Camundongos , Simulação de Dinâmica Molecular , Proteínas Nucleares/química , Proteínas Nucleares/classificação , Proteínas Nucleares/genética , Conformação de Ácido Nucleico , Pan troglodytes , Filogenia , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Alinhamento de Sequência
17.
Cureus ; 10(12): e3698, 2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30761246

RESUMO

Treatment of Fournier's gangrene often requires extensive surgical debridements that can ultimately necessitate penile amputation. Reconstruction can be challenging as these patients tend to have medical comorbidities deeming them poor microsurgical candidates. Fournier's gangrene resulting in penectomy is an infrequent occurrence, and treatment with phalloplasty is rarely described in the literature. Herein, we present a case of a 60-year-old male with poorly controlled diabetes mellitus who developed Fournier's gangrene in July 2017. His treatment course included multiple surgical debridements without resolution, eventually necessitating a penectomy. The patient elected for surgical reconstruction and underwent a phalloplasty procedure utilizing a radial forearm free flap. This case demonstrates a rare case of Fournier's gangrene resulting in penectomy with a unique reconstruction utilizing a radial forearm free flap in a poor microsurgical candidate.

18.
Plast Reconstr Surg Glob Open ; 5(9): e1458, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29062639

RESUMO

Supplemental Digital Content is available in the text.

19.
20.
Science ; 356(6339): 757-759, 2017 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-28522536

RESUMO

Insulin-like growth factor 2 (IGF2) is the major fetal growth hormone in mammals. We identify zinc finger protein 568 (ZFP568), a member of the rapidly evolving Kruppel-associated box-zinc finger protein (KRAB-ZFP) family linked primarily to silencing of endogenous retroelements, as a direct repressor of a placental-specific Igf2 transcript (designated Igf2-P0) in mice. Loss of Zfp568, which causes gastrulation failure, or mutation of the ZFP568-binding site at the Igf2-P0 promoter causes inappropriate Igf2-P0 activation. Deletion of Igf2 can completely rescue Zfp568 gastrulation phenotypes through late gestation. Our data highlight the exquisite selectivity with which members of the KRAB-ZFP family repress their targets and identify an additional layer of transcriptional control of a key growth factor regulating fetal and placental development.


Assuntos
Embrião de Mamíferos/metabolismo , Fator de Crescimento Insulin-Like II/deficiência , Fator de Crescimento Insulin-Like II/genética , Proteínas Nucleares/metabolismo , Animais , Feminino , Gastrulação/genética , Regulação da Expressão Gênica , Camundongos , Camundongos Knockout , Mutação , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Placenta/metabolismo , Gravidez , Regiões Promotoras Genéticas/genética , Proteínas Repressoras/metabolismo
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