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1.
Hum Mol Genet ; 33(9): 787-801, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38280229

RESUMO

Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, in which spinal curvature develops in adolescence, and 90% of patients are female. Scoliosis is a debilitating disease that often requires bracing or surgery in severe cases. AIS affects 2%-5.2% of the population; however, the biological origin of the disease remains poorly understood. In this study, we aimed to determine the function of a highly conserved genomic region previously linked to AIS using a mouse model generated by CRISPR-CAS9 gene editing to knockout this area of the genome to understand better its contribution to AIS, which we named AIS_CRMΔ. We also investigated the upstream factors that regulate the activity of this enhancer in vivo, whether the spatial expression of the LBX1 protein would change with the loss of AIS-CRM function, and whether any phenotype would arise after deletion of this region. We found a significant increase in mRNA expression in the developing neural tube at E10.5, and E12.5, for not only Lbx1 but also other neighboring genes. Adult knockout mice showed vertebral rotation and proprioceptive deficits, also observed in human AIS patients. In conclusion, our study sheds light on the elusive biological origins of AIS, by targeting and investigating a highly conserved genomic region linked to AIS in humans. These findings provide valuable insights into the function of the investigated region and contribute to our understanding of the underlying causes of this debilitating disease.


Assuntos
Escoliose , Animais , Camundongos , Humanos , Adolescente , Feminino , Masculino , Escoliose/genética , Rotação , Coluna Vertebral , Fenótipo , Genômica
2.
Dev Biol ; 509: 28-42, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38342399

RESUMO

The early stages of regeneration after injury are similar to those of wound healing. The ascidian Botrylloides diegensis can regenerate an entire adult from a small fragment of vascular tunic following the removal of all zooids in an injury-induced regeneration model. We investigated the molecular and cellular changes following injury to determine the differences between the healing process and the initiation of whole-body regeneration (WBR). We conducted transcriptome analysis at specific time points during regeneration and wound healing to identify differentially expressed genes (DEGs) and the unique biological processes associated with each state. Our findings revealed 296 DEGs at 10 h post-injury (hpi), with 71 highly expressed in healed tissue and 225 expressed during the WBR process. These DEGs were predicted to play roles in tissue reorganization, integrin signaling, extracellular matrix organization, and the innate immune system. Pathway analysis of the upregulated genes in the healed tunic indicated functional enrichment related to tissue repair, as has been observed in other species. Additionally, we examined the cell types in the tunic and ampullae in both tissue states using histology and in situ hybridization for six genes identified by transcriptome analysis. We observed strong mRNA expression in cells within the WBR tunic, and in small RNA-positive granules near the tunic edge. We hypothesized that many of these genes function in the compaction of the ampullae tunic, which is a pivotal process for WBR and dormancy in B. diegensis, and in an immune response. These findings establish surprising similarities between ascidian regeneration and human wound healing, emphasizing the potential for future investigations into human regenerative and repair mechanisms. This study provides valuable insights into the gene sets specifically activated during regeneration compared to wound healing, shedding light on the divergent activities of these processes.


Assuntos
Urocordados , Animais , Humanos , Urocordados/genética , Perfilação da Expressão Gênica , Transdução de Sinais , Cicatrização/genética
3.
Mol Cell Biochem ; 479(2): 297-311, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37059894

RESUMO

Many advances in small RNA-seq technology and bioinformatics pipelines have been made recently, permitting the discovery of novel miRNAs in the embryonic day 15.5 (E15.5) mouse brain. We aimed to improve miRNA discovery in this tissue to expand our knowledge of the regulatory networks that underpin normal neurodevelopment, find new candidates for neurodevelopmental disorder aetiology, and deepen our understanding of non-coding RNA evolution. A high-quality small RNA-seq dataset of 458 M reads was generated. An unbiased miRNA discovery pipeline identified fifty putative novel miRNAs, six of which were selected for further validation. A combination of conservation analysis and target functional prediction was used to determine the authenticity of novel miRNA candidates. These findings demonstrate that miRNAs remain to be discovered, particularly if they have the features of other small RNA species.


Assuntos
MicroRNAs , Animais , Camundongos , MicroRNAs/genética , Biologia Computacional , RNA-Seq , Encéfalo
4.
Diabetes Obes Metab ; 26(8): 3009-3019, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38637978

RESUMO

AIMS: To perform a systematic review of studies that sought to identify diagnostic biomarkers for the diagnosis of cardiovascular diseases (CVDs) and diabetes mellitus (DM), which could be used in low- and middle-income countries (LMICs) where there is a lack of diagnostic equipment, treatments and training. MATERIALS AND METHODS: Papers were sourced from six databases: the British Nursing Index, Google Scholar, PubMed, Sage, Science Direct and Scopus. Articles published between January 2002 and January 2023 were systematically reviewed by three reviewers and appropriate search terms and inclusion/exclusion criteria were applied. RESULTS: A total of 18 studies were yielded, as well as 234 diagnostic biomarkers (74 for CVD and 160 for DM). Primary biomarkers for the diagnosis of CVDs included growth differentiation factor 15 and neurogenic locus notch homologue protein 1 (Notch1). For the diagnosis of DM, alpha-2-macroglobulin, C-peptides, isoleucine, glucose, tyrosine, linoleic acid and valine were frequently reported across the included studies. Advanced analytical techniques, such as liquid chromatography mass spectrometry, enzyme-linked immunosorbent assays and vibrational spectroscopy, were also repeatedly reported in the included studies and were utilized in combination with traditional and alternative matrices such as fingernails, hair and saliva. CONCLUSIONS: While advanced analytical techniques are expensive, laboratories in LMICs should carry out a cost-benefit analysis of their use. Alternatively, laboratories may want to explore emerging techniques such as infrared, Fourier transform-infrared and near-infrared spectroscopy, which allow sensitive noninvasive analysis.


Assuntos
Biomarcadores , Doenças Cardiovasculares , Diabetes Mellitus , Humanos , Biomarcadores/análise , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/sangue , Fator 15 de Diferenciação de Crescimento/sangue , Fator 15 de Diferenciação de Crescimento/análise , Receptor Notch1
5.
Hum Mol Genet ; 29(22): 3717-3728, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33105483

RESUMO

Talipes equinovarus (clubfoot, TEV) is a congenital rotational foot deformity occurring in 1 per 1000 births with increased prevalence in males compared with females. The genetic etiology of isolated clubfoot (iTEV) remains unclear. Using a genome-wide association study, we identified a locus within FSTL5, encoding follistatin-like 5, significantly associated with iTEV. FSTL5 is an uncharacterized gene whose potential role in embryonic and postnatal development was previously unstudied. Utilizing multiple model systems, we found that Fstl5 was expressed during later stages of embryonic hindlimb development, and, in mice, expression was restricted to the condensing cartilage anlage destined to form the limb skeleton. In the postnatal growth plate, Fstl5 was specifically expressed in prehypertrophic chondrocytes. As Fstl5 knockout rats displayed no gross malformations, we engineered a conditional transgenic mouse line (Fstl5LSL) to overexpress Fstl5 in skeletal osteochondroprogenitors. We observed that hindlimbs were slightly shorter and that bone mineral density was reduced in adult male, but not female, Prrx1-cre;Fstl5LSL mice compared with control. No overt clubfoot-like deformity was observed in Prrx1-cre;Fstl5LSL mice, suggesting FSTL5 may function in other cell types to contribute to iTEV pathogenesis. Interrogating published mouse embryonic single-cell expression data showed that Fstl5 was expressed in cell lineage subclusters whose transcriptomes were associated with neural system development. Moreover, our results suggest that lineage-specific expression of the Fstl genes correlates with their divergent roles as modulators of transforming growth factor beta and bone morphogenetic protein signaling. Results from this study associate FSTL5 with iTEV and suggest a potential sexually dimorphic role for Fstl5 in vivo.


Assuntos
Pé Torto Equinovaro/genética , Proteínas Relacionadas à Folistatina/genética , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Animais , Pé Torto Equinovaro/patologia , Modelos Animais de Doenças , Extremidades/patologia , Regulação da Expressão Gênica/genética , Técnicas de Inativação de Genes , Estudos de Associação Genética , Humanos , Camundongos , Ratos
6.
Mol Reprod Dev ; 90(5): 295-309, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37084273

RESUMO

Understanding the molecular pathways that underpin ovarian development and function is vital for improving the research approaches to investigating fertility. Despite a significant improvement in our knowledge of molecular activity in the ovary, many questions remain unanswered in the quest to understand factors influencing fertility and ovarian pathologies such as cancer. Here, we present an investigation into the expression and function of the developmental transcription factor LIM Homeobox 9 (LHX9) in the adult mouse ovary. We have characterized Lhx9 expression in several cell types of the mature ovary across follicle stages. To evaluate possible LHX9 function in the adult ovary, we investigated ovarian anatomy and transcription in an Lhx9+/- knockout mouse model displaying subfertility. Despite a lack of gross anatomical differences between genotypes, RNA-sequencing found that 90 differentially expressed genes between Lhx9+/ - and Lhx9+/+ mice. Gene ontology analyses revealed a reduced expression of genes with major roles in ovarian steroidogenesis and an increased expression of genes associated with ovarian cancer. Analysis of the ovarian epithelium revealed Lhx9+/ - mice have a disorganized epithelial phenotype, corresponding to a significant increase in epithelial marker gene expression. These results provide an analysis of Lhx9 in the adult mouse ovary, suggesting a role in fertility and ovarian epithelial cancer.


Assuntos
Proteínas de Homeodomínio , Ovário , Feminino , Camundongos , Animais , Proteínas de Homeodomínio/genética , Ovário/metabolismo , Sequência de Bases , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Análise de Sequência de RNA , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo
7.
J Pers ; 91(1): 180-192, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35778899

RESUMO

INTRODUCTION: Cori Bush is a prominent modern activist in the U.S., becoming involved in activism following Michael Brown's death. Bush, like many activists before her, has set clear goals for social change, yet work is needed to understand why Bush (and like others) became an activist when others did not. One potential reason may be that these exemplars found purpose in life in activism. Thus, the current psychobiography explores the purpose in life of Cori Bush, a prominent activist and politician in the U.S., as well as what factors emerge for how Bush found her purpose in life. METHOD: The present research gathered public materials (e.g., speeches) from Bush and coded materials for the presence and depth of both themes of purpose and factors predicting purpose. RESULTS: Activism was the most prominent theme of purpose for Bush, with some pro-social purposes also occurring. Multiple personal factors emerged as influences on her activist purpose, including extraversion, psychological flexibility, and action-oriented coping style. Additionally, the situational factors of discriminatory experiences and Michael Brown's death emerged as factors. CONCLUSION: These results suggest that Bush has an activist purpose in life and that she found this purpose through a combination of personal and situational factors.


Assuntos
Adaptação Psicológica , Feminino , Humanos
8.
Differentiation ; 123: 30-41, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34906895

RESUMO

Adolescent Idiopathic Scoliosis (AIS) is the most common type of spine deformity affecting 2-3% of the population worldwide. The etiology of this disease is still poorly understood. Several GWAS studies have identified single nucleotide polymorphisms (SNPs) located near the gene LBX1 that is significantly correlated with AIS risk. LBX1 is a transcription factor with roles in myocyte precursor migration, cardiac neural crest specification, and neuronal fate determination in the neural tube. Here, we further investigated the role of LBX1 in the developing spinal cord of mouse embryos using a CRISPR-generated mouse model expressing a truncated version of LBX1 (Lbx1Δ). Homozygous mice died at birth, likely due to cardiac abnormalities. To further study the neural tube phenotype, we used RNA-sequencing to identify 410 genes differentially expressed between the neural tubes of E12.5 wildtype and Lbx1Δ/Δ embryos. Genes with increased expression in the deletion line were involved in neurogenesis and those with broad roles in embryonic development. Many of these genes have also been associated with scoliotic phenotypes. In comparison, genes with decreased expression were primarily involved in skeletal development. Subsequent skeletal and immunohistochemistry analysis further confirmed these results. This study aids in understanding the significance of links between LBX1 function and AIS susceptibility.


Assuntos
Proteínas de Homeodomínio , Escoliose , Animais , Proteínas de Homeodomínio/genética , Camundongos , Fenótipo , Polimorfismo de Nucleotídeo Único , Escoliose/genética , Fatores de Transcrição/genética
9.
Psychol Health Med ; 28(10): 3107-3116, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37332156

RESUMO

Given the increased threats to health and well-being faced by transgender individuals, research is needed to understand potential protective factors. Recent work has suggested that a sense of purpose may be one of the health-promoting resources available to marginalized groups, and levels of purpose are often similar or even higher among these groups. However, research is limited regarding whether this factor manifests differently among transgender adults. The current study (n = 1968 U.S. adults; 4.3% identified as transgender) asked participants to complete surveys for sense of purpose, self-rated health, life satisfaction and the type of purposes they deemed important. The findings suggest no difference in levels of sense of purpose between transgender and non-transgender adults. Transgender adults reported slightly lower levels of importance across multiple purposes, which merits further investigation into whether they perceive greater obstacles toward those goals. Of central importance, sense of purpose positively correlated with self-rated health (r = .50) and life satisfaction for transgender adults (r = .77), at similar or even greater magnitudes than for the non-transgender adults. These results point to the potential of exploring sense of purpose as an intervention target for promoting transgender health and well-being, and future directions should focus on the multiple pathways by which transgender identity may influence purpose development.


Assuntos
Pessoas Transgênero , Adulto , Humanos , Estados Unidos/epidemiologia , Identidade de Gênero , Inquéritos e Questionários , Fatores de Risco
10.
J Fish Biol ; 102(5): 1088-1095, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36856227

RESUMO

Otolith microstructure analysis provides critical biological and ecological information about the early life history of fishes. This information is particularly important to interpret and predict population dynamics for socio-economically important fisheries species; nonetheless, several key assumptions underpin the use of otolith techniques. The authors validated the use of this analysis for cabezon (Scorpaenichthys marmoratus; Ayres, 1854), a long-lived, large-bodied cottid constituent of nearshore fisheries from Baja California, Mexico, to Alaska, USA. To test three critical assumptions, the authors coupled otolith and morphometric analyses from an opportunistic rearing study of cabezon eggs and larvae with a long-term time series of juvenile cabezon field collections. The authors confirmed the daily otolith increment deposition in laboratory-reared larvae, identified the timing of first otolith increment deposition and examined the relationship between otolith growth and somatic growth in field-collected juveniles, validating the use of otolith microstructure analysis in biological and ecological interpretations of early life-history traits for this species. The findings of this study also indicated that the absorption of yolk-sac reserves, and likely the transition to exogenous feeding, plays an important role in regulating otolith increment deposition. Finally, the authors found within-brood size-at-age variation, which may be an advantage for young fish in prey-limited environments.


Assuntos
Membrana dos Otólitos , Perciformes , Animais , Larva , Membrana dos Otólitos/química , México , Peixes/fisiologia
11.
J Perianesth Nurs ; 38(6): 845-850, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37589630

RESUMO

PURPOSE: The use of lung protective ventilation (LPV) during general anesthesia is an effective strategy among certified registered nurse anesthetists (CRNAs) to reduce and prevent the incidence of postoperative pulmonary complications. The purpose of this project was to implement a LPV protocol, assess CRNA provider adherence, and investigate differences in ventilation parameters and postoperative oxygen requirements. DESIGN: This quality improvement project was conducted using a pre- and postimplementation design. METHODS: Sixty patients undergoing robotic laparoscopic abdominal surgery and 35 CRNAs at a community hospital participated. An evidence-based intraoperative LPV protocol was developed, CRNA education was provided, and the protocol was implemented. Pre- and postimplementation, CRNA knowledge, and confidence were assessed. Ventilation data were collected at 1-minute intervals intraoperatively and oxygen requirements were recorded in the postanesthesia care unit (PACU). FINDINGS: Use of intraoperative LPV strategies increased 2.4%. Overall CRNA knowledge (P = .588), confidence (P = .031), and practice (P < .001) improved from pre- to postimplementation. Driving pressures decreased from pre- to postimplementation (P < .001). Supplemental oxygen use on admission to the PACU decreased from 93.3% to 70.0%. CONCLUSIONS: Educational interventions and implementation of a standardized protocol can improve the use of intraoperative LPV strategies and patient outcomes.


Assuntos
Enfermeiros Anestesistas , Respiração Artificial , Humanos , RNA Complementar , Pulmão , Complicações Pós-Operatórias/prevenção & controle , Oxigênio
12.
Crit Rev Food Sci Nutr ; 62(18): 4982-4997, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33576691

RESUMO

Omega-3 (n-3) fatty acids offer a plethora of health benefits with the majority of evidence showing beneficial effects from marine sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Emerging research examines the effects of n-3 dietary intakes on blood markers of vegetarians and vegans, but official guidance for plant based marine alternatives is yet to reach consensus. This scoping review provides an overview of trials investigating bioavailability of plant n-3 oils including EPA and DHA conversion. Searches of MEDLINE, PubMed, CINAHL and clinical trial registers identified randomized controlled trials from January 2010 to September 2020. The 'Omega-3 index' (EPA + DHA (O3I)), was used to compare n-3 status, metabolic conversion and bioavailability. Two reviewers independently screened articles and extracted data on outcomes. From 639 identified articles, screening and eligibility checks gave 13 articles. High dose flaxseed or echium seed oil supplements, provided no increases to O3I and some studies showed reductions. However, microalgal oil supplementation increased O3I levels for all studies. Findings indicate preliminary advice for vegetarians and vegans is regular consumption of preformed EPA and DHA supplements may help maintain optimal O3I. Further studies should establish optimum EPA and DHA ratios and dosages in vegetarian and vegan populations.


Assuntos
Ácidos Graxos Ômega-3 , Veganos , Disponibilidade Biológica , Dieta Vegetariana , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Humanos , Vegetarianos
13.
Inorg Chem ; 60(6): 3572-3584, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33616393

RESUMO

The atomic-level tunability of molecular structures is a compelling reason to develop homogeneous catalysts for challenging reactions such as the electrochemical reduction of carbon dioxide to valuable C1-Cn products. Of particular interest is methane, the largest component of natural gas. Herein, we report a series of three isomeric rhenium tricarbonyl complexes coordinated by the asymmetric diimine ligands 2-(isoquinolin-1-yl)-4,5-dihydrooxazole (quin-1-oxa), 2-(quinolin-2-yl)-4,5-dihydrooxazole (quin-2-oxa), and 2-(isoquinolin-3-yl)-4,5-dihydrooxazole (quin-3-oxa) that catalyze the reduction of CO2 to carbon monoxide and methane, albeit the latter with a low efficiency. To our knowledge, these complexes are the first examples of rhenium(I) catalysts capable of converting carbon dioxide into methane. Re(quin-1-oxa)(CO)3Cl (1), Re(quin-2-oxa)(CO)3Cl (2), and Re(quin-3-oxa)(CO)3Cl (3) were characterized and studied using a variety of electrochemical and spectroscopic techniques. In bulk electrolysis experiments, the three complexes reduce CO2 to CO and CH4. When the controlled-potential electrolysis experiments are performed at -2.5 V (vs Fc+/0) and in the presence of the Brønsted acid 2,2,2-trifluoroethanol, methane is produced with turnover numbers that range from 1.3 to 1.8. Isotope labeling experiments using 13CO2 atmosphere produce 13CH4 (m/z = 17) confirming that methane originates from CO2 reduction. Theoretical calculations are performed to investigate the mechanistic aspects of the 8e-/8H+ reduction of CO2 to CH4. A ligand-assisted pathway is proposed to be an efficient pathway in the formation of CH4. Delocalization of the electron density on the (iso)quinoline moiety upon reduction stabilizes the key carbonyl intermediate leading to additional reactivity of this ligand. These results should aid the development of more robust catalytic systems that produce CH4 from CO2.

14.
J Exp Biol ; 222(Pt 15)2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31253711

RESUMO

The colonial tunicate Botrylloides leachii is exceptional at regenerating from a piece of vascular tunic after loss of all adults from the colony. Previous transcriptome analyses indicate a brief period of healing before regeneration of a new adult (zooid) in as little as 8-10 days. However, there is little understanding of how the resulting changes to gene expression, required to drive regeneration, are initiated and how the overall process is regulated. Rapid changes to transcription often occur in response to chromatin changes, mediated by histone modifications such as histone acetylation. Here, we investigated a group of key epigenetic modifiers, histone deacetylases (HDAC), which are known to play an important role in many biological processes such as development, healing and regeneration. Through our transcriptome data, we identified and quantified the expression levels of HDAC and histone acetyltransferase enzymes during whole-body regeneration (WBR). To determine whether HDAC activity is required for WBR, we inhibited its action using valproic acid and trichostatin A. HDAC inhibition prevented the final morphological changes normally associated with WBR and resulted in aberrant gene expression. Botrylloides leachii genes including Slit2, TGF-ß, Piwi and Fzd4 all showed altered mRNA levels upon HDAC inhibition in comparison with the control samples. Additionally, atypical expression of Bl_Piwi was found in immunocytes upon HDAC inhibition. Together, these results show that HDAC function, specifically HDAC I/IIa class enzymes, are vital for B. leachii to undergo WBR successfully.


Assuntos
Histona Desacetilases/metabolismo , Regeneração , Urocordados/fisiologia , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/genética , Ácidos Hidroxâmicos/farmacologia , RNA Mensageiro , Urocordados/enzimologia , Urocordados/genética , Urocordados/metabolismo , Ácido Valproico/farmacologia
15.
J Eukaryot Microbiol ; 66(6): 882-891, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31033101

RESUMO

Holomastigotes is a protist genus (Parabasalia: Spirotrichonymphea) that resides in the hindguts of "lower" termites. It can be distinguished from other parabasalids by spiral flagellar bands that run along the entire length of the cell, an anterior nucleus, a reduced or absent axostyle, the presence of spherical vesicles inside the cells, and the absence of ingested wood particles. Eight species have been described based on their morphology so far, although no molecular data were available prior to this study. We determined the 18S rRNA gene sequences of Holomastigotes from the hindguts of Hodotermopsis sjostedti, Reticulitermes flavipes, Reticulitermes lucifugus, and Reticulitermes tibialis. Phylogenetic analyses placed all sequences in an exclusive and well-supported clade with the type species, Holomastigotes elongatum from R. lucifugus. However, the phylogenetic position of Holomastigotes within the Spirotrichonymphea was not resolved. We describe two new species, Holomastigotes flavipes n. sp. and Holomastigotes tibialis n. sp., inhabiting the hindguts of R. flavipes and R. tibialis, respectively.


Assuntos
Isópteros/parasitologia , Parabasalídeos/classificação , Animais , Sistema Digestório/parasitologia , Parabasalídeos/citologia , Parabasalídeos/genética , Filogenia , RNA de Protozoário/análise , RNA Ribossômico 18S/análise , Simbiose
16.
Am Fam Physician ; 99(11): 682-688, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150188

RESUMO

Varicose veins are twisted, dilated veins most commonly located on the lower extremities. The exact pathophysiology is debated, but it involves a genetic predisposition, incompetent valves, weakened vascular walls, and increased intravenous pressure. Risk factors include family history of venous disease; female sex; older age; chronically increased intra-abdominal pressure due to obesity, pregnancy, chronic constipation, or a tumor; and prolonged standing. Symptoms of varicose veins include a heavy, achy feeling and an itching or burning sensation; these symptoms worsen with prolonged standing. Potential complications include infection, leg ulcers, stasis changes, and thrombosis. Conservative treatment options include external compression; lifestyle modifications, such as avoidance of prolonged standing and straining, exercise, wearing nonrestrictive clothing, modification of cardiovascular risk factors, and interventions to reduce peripheral edema; elevation of the affected leg; weight loss; and medical therapy. There is not enough evidence to determine if compression stockings are effective in the treatment of varicose veins in the absence of active or healed venous ulcers. Interventional treatments include external laser thermal ablation, endovenous thermal ablation, endovenous sclerotherapy, and surgery. Although surgery was once the standard of care, it largely has been replaced by endovenous thermal ablation, which can be performed under local anesthesia and may have better outcomes and fewer complications than other treatments. Existing evidence and clinical guidelines suggest that a trial of compression therapy is not warranted before referral for endovenous thermal ablation, although it may be necessary for insurance coverage.


Assuntos
Varizes/diagnóstico , Varizes/terapia , Humanos , Varizes/etiologia
18.
19.
Am J Hum Genet ; 97(6): 837-47, 2015 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-26637977

RESUMO

The periosteum contributes to bone repair and maintenance of cortical bone mass. In contrast to the understanding of bone development within the epiphyseal growth plate, factors that regulate periosteal osteogenesis have not been studied as intensively. Osteofibrous dysplasia (OFD) is a congenital disorder of osteogenesis and is typically sporadic and characterized by radiolucent lesions affecting the cortical bone immediately under the periosteum of the tibia and fibula. We identified germline mutations in MET, encoding a receptor tyrosine kinase, that segregate with an autosomal-dominant form of OFD in three families and a mutation in a fourth affected subject from a simplex family and with bilateral disease. Mutations identified in all families with dominant inheritance and in the one simplex subject with bilateral disease abolished the splice inclusion of exon 14 in MET transcripts, which resulted in a MET receptor (MET(Δ14)) lacking a cytoplasmic juxtamembrane domain. Splice exclusion of this domain occurs during normal embryonic development, and forced induction of this exon-exclusion event retarded osteoblastic differentiation in vitro and inhibited bone-matrix mineralization. In an additional subject with unilateral OFD, we identified a somatic MET mutation, also affecting exon 14, that substituted a tyrosine residue critical for MET receptor turnover and, as in the case of the MET(Δ14) mutations, had a stabilizing effect on the mature protein. Taken together, these data show that aberrant MET regulation via the juxtamembrane domain subverts core MET receptor functions that regulate osteogenesis within cortical diaphyseal bone.


Assuntos
Doenças do Desenvolvimento Ósseo/genética , Éxons , Mutação em Linhagem Germinativa , Osteogênese/genética , Periósteo/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Adulto , Sequência de Bases , Doenças do Desenvolvimento Ósseo/metabolismo , Doenças do Desenvolvimento Ósseo/patologia , Diferenciação Celular , Criança , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Genes Dominantes , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Osteoblastos/metabolismo , Osteoblastos/patologia , Linhagem , Periósteo/crescimento & desenvolvimento , Periósteo/patologia , Cultura Primária de Células , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-met/metabolismo , Splicing de RNA
20.
Can Vet J ; 58(12): 1281-1286, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29203937

RESUMO

This prospective study evaluated the handling, intraoperative and postoperative complication rates of a barbed knotless suture for closure of subcutaneous tissue and skin in 17 client-owned dogs (group A) following a tibial plateau leveling osteotomy procedure. Clinical characteristics, surgical time, and complication rates were compared to a control group of 17 client-owned dogs (group B) with subcutaneous tissue and skin closure using traditional suture material. Signalment was not significantly different between groups and did not have an effect on complication rates. Surgical times were not significantly different for subcutaneous tissue or skin closure between the 2 groups. There were significantly more intraoperative complications in the barbed suture group (A: 4/17; B: 0/17; P = 0.033) but no difference in minor or major postoperative complication rates (minor A: 2/16; B: 1/14; P = 0.626, major A: 2/16; B: 0/14; P = 0.171).


Comparaison du temps opératoire et du taux de complication de la fermeture sous-cutanée et de la peau en utilisant des points de suture barbelés ou des points de suture noués traditionnels chez les chiens. Cette étude prospective a évalué les taux de complication liés à la manipulation, peropératoire et postopératoire des points de suture barbelés sans noeuds pour la fermeture du tissu sous-cutané et de la peau chez 17 chiens appartenant à des clients (groupe A) après une intervention d'ostéotomie de nivellement du plateau tibial. Les caractéristiques cliniques, le temps opératoire et les taux de complication ont été comparés à un groupe témoin de 17 chiens appartenant à des clients (groupe B) avec du matériel de suture traditionnel pour la fermeture du tissus sous-cutanés et de la peau. Le signalement n'était pas significativement différent entre les groupes et n'a pas eu d'effet sur les taux de complication. Le temps opératoire n'était pas significativement différent pour la fermeture du tissu sous-cutané ou de la peau entre les deux groupes. Il y avait significativement plus de complications peropératoires dans le groupe à points de suture barbelés (A : 4/17; B : 0/17; P = 0,033) mais aucune différence pour les taux de complications postopératoires mineures ou majeures (mineure A : 2/16; B : 1/14; P = 0,626, majeure A : 2/16; B : 0/14; P = 0,171).(Traduit par Isabelle Vallières).


Assuntos
Cães/cirurgia , Técnicas de Sutura/veterinária , Suturas/veterinária , Técnicas de Fechamento de Ferimentos/veterinária , Animais , Feminino , Complicações Intraoperatórias/veterinária , Masculino , Duração da Cirurgia , Osteotomia/métodos , Osteotomia/veterinária , Complicações Pós-Operatórias/veterinária , Estudos Prospectivos , Técnicas de Sutura/efeitos adversos , Suturas/efeitos adversos , Tíbia/cirurgia , Técnicas de Fechamento de Ferimentos/efeitos adversos
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