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1.
J Proteome Res ; 23(5): 1744-1756, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38569191

RESUMEN

Early diagnosis of biliary atresia (BA) is crucial for improving the chances of survival and preserving the liver function of pediatric patients with BA. Herein, we performed proteomics analysis using data-independent acquisition (DIA) and parallel reaction monitoring (PRM) to explore potential biomarkers for the early diagnosis of BA compared to other non-BA jaundice cases. Consequently, we detected and validated differential protein expression in the plasma of patients with BA compared to the plasma of patients with intrahepatic cholestasis. Bioinformatics analysis revealed the enriched biological processes characteristic of BA by identifying the differential expression of specific proteins. Signaling pathway analysis revealed changes in the expression levels of proteins associated with an alteration in immunoglobulin levels, which is indicative of immune dysfunction in BA. The combination of polymeric immunoglobulin receptor expression and immunoglobulin lambda variable chain (IGL c2225_light_IGLV1-47_IGLJ2), as revealed via machine learning, provided a useful early diagnostic model for BA, with a sensitivity of 0.8, specificity of 1, accuracy of 0.89, and area under the curve value of 0.944. Thus, our study identified a possible effective plasma biomarker for the early diagnosis of BA and could help elucidate the underlying mechanisms of BA.


Asunto(s)
Atresia Biliar , Biomarcadores , Diagnóstico Precoz , Proteómica , Atresia Biliar/diagnóstico , Atresia Biliar/sangre , Humanos , Biomarcadores/sangre , Proteómica/métodos , Femenino , Lactante , Masculino , Biología Computacional/métodos , Aprendizaje Automático , Sensibilidad y Especificidad
2.
Bone Joint J ; 106-B(2): 144-150, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38425304

RESUMEN

Aims: The aim of this study was to determine both the incidence of, and the reoperation rate for, postoperative periprosthetic femoral fracture (POPFF) after total hip arthroplasty (THA) with either a collared cementless (CC) femoral component or a cemented polished taper-slip (PTS) femoral component. Methods: We performed a retrospective review of a consecutive series of 11,018 THAs over a ten-year period. All POPFFs were identified using regional radiograph archiving and electronic care systems. Results: A total of 11,018 THAs were implanted: 4,952 CC femoral components and 6,066 cemented PTS femoral components. Between groups, age, sex, and BMI did not differ. Overall, 91 patients (0.8%) sustained a POPFF. For all patients with a POPFF, 16.5% (15/91) were managed conservatively, 67.0% (61/91) underwent open reduction and internal fixation (ORIF), and 16.5% (15/91) underwent revision. The CC group had a lower POPFF rate compared to the PTS group (0.7% (36/4,952) vs 0.9% (55/6,066); p = 0.345). Fewer POPFFs in the CC group required surgery (0.4% (22/4,952) vs 0.9% (54/6,066); p = 0.005). Fewer POPFFs required surgery in males with a CC than males with a PTS (0.3% (7/2,121) vs 1.3% (36/2,674); p < 0.001). Conclusion: Male patients with a PTS femoral component were five times more likely to have a reoperation for POPFF. Female patients had the same incidence of reoperation with either component type. Of those having a reoperation, 80.3% (61/76) had an ORIF, which could greatly mask the size of this problem in many registries.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Fracturas Periprotésicas , Humanos , Masculino , Femenino , Artroplastia de Reemplazo de Cadera/efectos adversos , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Prótesis de Cadera/efectos adversos , Reoperación/efectos adversos , Factores de Riesgo , Diseño de Prótesis , Cementos para Huesos , Estudios Retrospectivos
3.
Proc Inst Mech Eng H ; 238(3): 324-331, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38235693

RESUMEN

This biomechanical study aimed to determine if variations in stem material, stem geometry, stem offset and cement viscosity affect mechanical resistance to postoperative periprosthetic fracture (PFF) after hip arthroplasty with a commonly used cemented polished taper-slip (PTS) stem (CPT, Zimmer Biomet) in a novel osteoporotic composite femoral bone model. Thirty-six osteoporotic composite femoral models were tested using a standardised in-vitro loading technique to simulate a typical PFF. Outcome measures were torque to failure (N), fracture energy (N/m2) and rotation to failure (°). Comparisons were made by stem material (cobalt chrome vs stainless steel), stem geometry (CPT stem vs Exeter stem), stem offset (standard offset vs extra extended offset) and cement viscosity (high viscosity vs low viscosity). Statistical comparisons were carried out with significance set at p < 0.05. All tested samples produced clinically representative fracture patterns with varying degrees of bone and cement comminution. There was no statistically significant difference in torque to failure, fracture energy or rotation to failure between any of the compared variables (all p > 0.05). This is the first biomechanical study on mechanical resistance to PFF using osteoporotic composite bone models. For the CPT stem, it confirms that stem material, stem offset, stem geometry and cement viscosity do not affect mechanical resistance to PFF in an osteoporotic bone model.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Fémur , Prótesis de Cadera , Fracturas Periprotésicas , Humanos , Fracturas Periprotésicas/cirugía , Fracturas Periprotésicas/complicaciones , Artroplastia de Reemplazo de Cadera/efectos adversos , Prótesis de Cadera/efectos adversos , Diseño de Prótesis , Factores de Riesgo , Cementos para Huesos , Fracturas del Fémur/cirugía , Reoperación/efectos adversos
4.
Bone Joint J ; 106-B(1): 11-15, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38160687

RESUMEN

Polished taper-slip (PTS) cemented stems have an excellent clinical track record and are the most common stem type used in primary total hip arthroplasty (THA) in the UK. Due to low rates of aseptic loosening, they have largely replaced more traditional composite beam (CB) cemented stems. However, there is now emerging evidence from multiple joint registries that PTS stems are associated with higher rates of postoperative periprosthetic femoral fracture (PFF) compared to their CB stem counterparts. The risk of both intraoperative and postoperative PFF remains greater with uncemented stems compared to either of these cemented stem subtypes. PFF continues to be a devastating complication following primary THA and is associated with high complication and mortality rates. Recent efforts have focused on identifying implant-related risk factors for PFF in order to guide preventative strategies, and therefore the purpose of this article is to present the current evidence on the effect of cemented femoral stem design on the risk of PFF.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Fémur , Prótesis de Cadera , Fracturas Periprotésicas , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Prótesis de Cadera/efectos adversos , Reoperación/efectos adversos , Diseño de Prótesis , Factores de Riesgo , Fracturas del Fémur/etiología , Fracturas del Fémur/cirugía
5.
PLoS Biol ; 21(7): e3002191, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37463141

RESUMEN

We study natural DNA polymorphisms and associated phenotypes in the Arabidopsis relative Cardamine hirsuta. We observed strong genetic differentiation among several ancestry groups and broader distribution of Iberian relict strains in European C. hirsuta compared to Arabidopsis. We found synchronization between vegetative and reproductive development and a pervasive role for heterochronic pathways in shaping C. hirsuta natural variation. A single, fast-cycling ChFRIGIDA allele evolved adaptively allowing range expansion from glacial refugia, unlike Arabidopsis where multiple FRIGIDA haplotypes were involved. The Azores islands, where Arabidopsis is scarce, are a hotspot for C. hirsuta diversity. We identified a quantitative trait locus (QTL) in the heterochronic SPL9 transcription factor as a determinant of an Azorean morphotype. This QTL shows evidence for positive selection, and its distribution mirrors a climate gradient that broadly shaped the Azorean flora. Overall, we establish a framework to explore how the interplay of adaptation, demography, and development shaped diversity patterns of 2 related plant species.


Asunto(s)
Arabidopsis , Cardamine , Arabidopsis/genética , Cardamine/genética , Genotipo , Fenotipo , Demografía
6.
J Hepatol ; 77(5): 1299-1310, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35803543

RESUMEN

BACKGROUND & AIMS: We have previously reported on the potential pathogenic role of neutrophils in biliary atresia (BA). Herein, we aimed to delineate the role of CD177+ neutrophils in the pathogenesis of BA. METHODS: Immune cells from the livers of mice with rhesus rotavirus-induced BA were analysed. Single-cell RNA-sequencing was performed to specifically analyse Gr-1+ (Ly6C/Ly6G+) cells in the liver. Gene expression profiles of CD177+ cells were analysed using the Smart-Seq RNA-sequencing method, and the pathogenesis of BA was examined in Cd177-/- mice. Neutrophil extracellular trap (NET) inhibitors were used to determine the role of CD177+ cell-derived NETs in BA-associated bile duct damage, and a pilot clinical study evaluated the potential effects of N-acetylcysteine on NET release in BA. RESULTS: Increased levels of Gr-1+ cells were observed in the livers of mice with rhesus rotavirus-induced BA. RNA-sequencing analysis revealed that CD177+ cells were the main population of Gr-1+ cells and expressed elevated levels of both interferon-stimulated and neutrophil degranulation genes. Cd177-/- BALB/c mice exhibited delayed disease onset and reduced morbidity and mortality. High numbers of mitochondria were detected in CD177+ cells derived from mice with BA; these cells were associated with increased levels of reactive oxygen species and increased NET formation, which induced the apoptosis of biliary epithelial cells in cocultures. In a pilot clinical study, the administration of N-acetylcysteine to patients with BA reduced CD177+ cell numbers and reactive oxygen species levels, indicating a potential beneficial effect. CONCLUSIONS: Our data indicate that CD177+ cells play an important role in the initiation of BA pathogenesis via NET formation. CLINICAL TRIAL REGISTRATION: The pilot study of N-acetylcysteine treatment in patients with BA was registered on the Chinese Clinical Trial Registry (ChiCTR2000040505). LAY SUMMARY: Neutrophils (a type of innate immune cell, i.e. an immune cell that doesn't target a specific antigen) are thought to play a role in the development of biliary atresia (a rare but potentially lethal condition of the bile ducts that occurs in infants). Herein, we found that neutrophils expressing a particular protein (CD177) played an important role in bile duct damage by releasing a special structure (NET) that can trap and kill pathogens but that can also cause severe tissue damage. A pilot study in patients with biliary atresia showed that inhibiting NETs could have a beneficial effect.


Asunto(s)
Atresia Biliar , Trampas Extracelulares , Rotavirus , Acetilcisteína , Animales , Atresia Biliar/patología , Modelos Animales de Enfermedad , Interferones , Ratones , Ratones Endogámicos BALB C , Proyectos Piloto , ARN , Especies Reactivas de Oxígeno , Rotavirus/genética
7.
Proc Inst Mech Eng H ; 236(7): 973-978, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35603754

RESUMEN

Postoperative periprosthetic femoral fracture following hip replacement has been the subject of many varied experimental approaches. Cadaveric samples offer realistic fit and fracture patterns but are subject to large between-sample variation. Composite femurs have not yet been validated for this purpose. We compared the results of composite femurs to cadaveric femurs using an established methodology. In vitro postoperative periprosthetic fracture results using axial-rotational loading were compared between 12 composite femurs and nine fresh frozen femurs, which were implanted with an otherwise identical collarless (6 composite vs 4 cadaveric) or collared (6 composite vs 5 cadaveric) cementless femoral stem using identical methodology. Fracture torque and rotational displacement were measured and torsional stiffness and rotational work prior to fracture were estimated. Fractures patterns were graded according to the Unified Classification System. Fracture torque, displacement, torsional stiffness and fracture patterns for cadaveric and composite femurs were similar between groups. There was a trend for a greater rotational displacement in the cadaveric groups, which lead to a decrease in torsional stiffness and a significantly greater rotational work prior to fracture for all cadaveric specimens (collarless stems: 10.51 [9.71 to 12.57] vs 5.21 [4.25 to 6.04], p = 0.01 and for collared stems: 15.38 [14.01 to 17.05] vs 5.76 [4.92 to 6.64], p = 0.01). Given comparable fracture torque and the similarity in fracture patterns for fracture trials using composite samples versus cadaveric femurs, the use of composite femur models may be a reasonable choice for postoperative periprosthetic femoral fracture studies within certain limitations.


Asunto(s)
Fracturas del Fémur , Prótesis de Cadera , Fracturas Periprotésicas , Fenómenos Biomecánicos , Cadáver , Fracturas del Fémur/cirugía , Fémur/cirugía , Humanos , Fracturas Periprotésicas/cirugía
8.
Front Immunol ; 13: 820524, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35222397

RESUMEN

P2Y1 receptor is a G-protein-coupled receptor that plays a critical role in the immune response of inflammatory bowel diseases. However, its regulatory effects on CD4+ T cell response have not been fully elucidated. The study aimed to characterize the role of P2Y1R in Th17 cell differentiation and colonic inflammation. Our results demonstrated that P2Y1R was significantly increased in the splenocytes of colitic mice, which was positively associated with the expression of RORγt and IL-17A. P2Y1R deficiency significantly ameliorated DSS-induced colitis and its Th17 responses. In parallel, P2Y1R deficiency greatly impaired the differentiation of Th17 cell, down-regulated the mRNA expression of IL-17A and RORγt, and protein expression of RORγt in vitro. More importantly, it was found that P2Y1R deficiency markedly increased AMPK phosphorylation of Th17 polarized CD4+ T cells, and antagonist of AMPK significantly reversed the inhibitory effect of P2Y1R deficiency on Th17 cell generation in vivo and in vitro. Overall, these findings demonstrated that P2Y1R deficiency could suppress Th17 cell differentiation in an AMPK-dependent manner to ameliorate colitis, and P2Y1R can act as an important regulator of Th17 cell differentiation to control colonic inflammation.


Asunto(s)
Colitis , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Diferenciación Celular , Colitis/inducido químicamente , Colitis/metabolismo , Inflamación/metabolismo , Interleucina-17/metabolismo , Ratones , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Células Th17
9.
Injury ; 53(2): 645-652, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34893307

RESUMEN

BACKGROUND: This multicentre case-control study compares Vancouver Classification System (VCS) grade and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture type in interprosthetic femoral fractures (IPFFs) between primary total hip arthroplasty (THA) and ipsilateral total knee arthroplasty (TKA) to periprosthetic femoral fracture (PFF) without ipsilateral TKA. METHODS: Data were collected following institutional approval. Eighty-four IPFFs were assessed for VCS grade and AO/OTA type. Each IPFF case (84) was matched to five PFF controls (360) by age, gender and stem fixation philosophy (SMD<0.1). VCS grade and AO/OTA type were compared between the IPFF and PFF groups using weighted proportions and medians. RESULTS: Median (IQR) age of IPFF patients was 81.75 (76.57-85.33) years and 61 (72.6%) were female. The commonest VCS grade was B1 (34, 40.5%). The commonest AO/OTA type was spiral (51.8% of VCS B fractures; 50.0% of VCS C fractures). A greater proportion of fractures occurred distal to the stem in IPFF patients versus PFF patients (33.3% versus 18.2%, p = 0.003). VCS grade was significantly different between groups (p = 0.015). For VCS C fractures, twice as many AO/OTA transverse and wedge fractures occurred in the IPFF group compared to the PFF group (25.0% versus 12.6% and 7.1% versus 3.3%, respectively) although the overall difference was not statistically significant (p = 0.407). CONCLUSION: The presence of an ipsilateral TKA affects the location of PFF with more fractures occurring distal to the stem. A greater proportion of bending type fractures occurred when an ipsilateral TKA was present. These unstable fractures often require more complex surgery.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Fracturas del Fémur , Fracturas Periprotésicas , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Estudios de Casos y Controles , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/epidemiología , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas , Humanos , Fracturas Periprotésicas/diagnóstico por imagen , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/cirugía , Reoperación , Estudios Retrospectivos
10.
J Arthroplasty ; 37(2): 398-405.e1, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34543696

RESUMEN

BACKGROUND: Postoperative periprosthetic fracture of the femur (POPFF) is associated with increased mortality. There is a lack of general estimates of mortality after POPFF and a need for higher-level evidence in this area. The aim of this study was to estimate mortality after POPFF using data reported in cohort studies from the last decade. METHODS: Literature search was conducted using Medline and Embase. The primary outcome was all-cause mortality during time as an inpatient, within 30 days, within 90 days, and within one year of POPFF. Mortality (95% confidence interval [CI]) was estimated using metaregression. RESULTS: A total of 4841 patients from 35 cohort studies were included. Study quality was generally low. The weighted mean follow-up was 2.3 years, and the most common POPFF was Vancouver B. The pooled mortality as an inpatient was 2.4% (95% CI 1.6% to 3.4%). The pooled mortality within 30 days was 3.3% (95% CI 2.0% to 5.0%). The pooled mortality within 90 days was 4.8% (95% CI 3.6% to 6.1%). The pooled mortality within one year was 13.4% (95% CI 11.9% to 14.8%). Mortality after POPFF was like that of neck of femur fracture up to 30 days, but better at one year. CONCLUSION: Mortality is like that experienced by patients after neck of femur fracture up to 30 days, but better at one year, which may represent the lower underlying risk of death in the POPFF cohort. These results may form the basis for evaluation of services treating POPFF in the future.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Fémur , Prótesis de Cadera , Fracturas Periprotésicas , Artroplastia de Reemplazo de Cadera/efectos adversos , Estudios de Cohortes , Fracturas del Fémur/epidemiología , Fracturas del Fémur/etiología , Fracturas del Fémur/cirugía , Fémur/cirugía , Humanos , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Reoperación , Estudios Retrospectivos
11.
Bone Joint J ; 103-B(8): 1339-1344, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34334039

RESUMEN

AIMS: This aim of this study was to assess the reliability and validity of the Unified Classification System (UCS) for postoperative periprosthetic femoral fractures (PFFs) around cemented polished taper-slip (PTS) stems. METHODS: Radiographs of 71 patients with a PFF admitted consecutively at two centres between 25 February 2012 and 19 May 2020 were collated by an independent investigator. Six observers (three hip consultants and three trainees) were familiarized with the UCS. Each PFF was classified on two separate occasions, with a mean time between assessments of 22.7 days (16 to 29). Interobserver reliability for more than two observers was assessed using percentage agreement and Fleiss' kappa statistic. Intraobserver reliability between two observers was calculated with Cohen kappa statistic. Validity was tested on surgically managed UCS type B PFFs where stem stability was documented in operation notes (n = 50). Validity was assessed using percentage agreement and Cohen kappa statistic between radiological assessment and intraoperative findings. Kappa statistics were interpreted using Landis and Koch criteria. All six observers were blinded to operation notes and postoperative radiographs. RESULTS: Interobserver reliability percentage agreement was 58.5% and the overall kappa value was 0.442 (moderate agreement). Lowest kappa values were seen for type B fractures (0.095 to 0.360). The mean intraobserver reliability kappa value was 0.672 (0.447 to 0.867), indicating substantial agreement. Validity percentage agreement was 65.7% and the mean kappa value was 0.300 (0.160 to 0.4400) indicating only fair agreement. CONCLUSION: This study demonstrates that the UCS is unsatisfactory for the classification of PFFs around PTS stems, and that it has considerably lower reliability and validity than previously described for other stem types. Radiological PTS stem loosening in the presence of PFF is poorly defined and formal intraoperative testing of stem stability is recommended. Cite this article: Bone Joint J 2021;103-B(8):1339-1344.


Asunto(s)
Fracturas del Fémur/clasificación , Prótesis de Cadera , Fracturas Periprotésicas/clasificación , Complicaciones Posoperatorias/clasificación , Anciano , Anciano de 80 o más Años , Cementos para Huesos , Femenino , Fracturas del Fémur/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Fracturas Periprotésicas/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Diseño de Prótesis , Radiografía , Reproducibilidad de los Resultados
12.
Bone Jt Open ; 2(7): 466-475, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34233455

RESUMEN

AIMS: This study evaluates risk factors influencing fracture characteristics for postoperative periprosthetic femoral fractures (PFFs) around cemented stems in total hip arthroplasty. METHODS: Data were collected for PFF patients admitted to eight UK centres between 25 May 2006 and 1 March 2020. Radiographs were assessed for Unified Classification System (UCS) grade and AO/OTA type. Statistical comparisons investigated relationships by age, gender, and stem fixation philosophy (polished taper-slip (PTS) vs composite beam (CB)). The effect of multiple variables was estimated using multinomial logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Surgical treatment (revision vs fixation) was compared by UCS grade and AO/OTA type. RESULTS: A total of 584 cases were included. Median age was 79.1 years (interquartile range 72.0 to 86.0), 312 (53.6%) patients were female, and 495 (85.1%) stems were PTS. The commonest UCS grade was type B1 (278, 47.6%). The most common AO/OTA type was spiral (352, 60.3%). Metaphyseal split fractures occurred only with PTS stems with an incidence of 10.1%. Male sex was associated with a five-fold reduction in odds of a type C fracture (OR 0.22 (95% CI 0.12 to 0.41); p < 0.001) compared to a type B fracture. CB stems were associated with significantly increased odds of transverse fracture (OR 9.51 (95% CI 3.72 to 24.34); p < 0.001) and wedge fracture (OR 3.72 (95% CI 1.16 to 11.95); p = 0.027) compared to PTS stems. Both UCS grade and AO/OTA type differed significantly (p < 0.001 and p = 0.001, respectively) between the revision and fixation groups but a similar proportion of B1 fractures underwent revision compared to fixation (45.3% vs 50.6%). CONCLUSION: The commonest fracture types are B1 and spiral fractures. PTS stems are exclusively associated with metaphyseal split fractures, but their incidence is low. Males have lower odds of UCS grade C fractures compared to females. CB stems have higher odds of bending type fractures (transverse and wedge) compared to PTS stems. There is considerable variation in practice when treating B1 fractures around cemented stems. Cite this article: Bone Jt Open 2021;2(7):466-475.

13.
Proc Natl Acad Sci U S A ; 118(23)2021 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-34088847

RESUMEN

B chromosomes are enigmatic elements in thousands of plant and animal genomes that persist in populations despite being nonessential. They circumvent the laws of Mendelian inheritance but the molecular mechanisms underlying this behavior remain unknown. Here we present the sequence, annotation, and analysis of the maize B chromosome providing insight into its drive mechanism. The sequence assembly reveals detailed locations of the elements involved with the cis and trans functions of its drive mechanism, consisting of nondisjunction at the second pollen mitosis and preferential fertilization of the egg by the B-containing sperm. We identified 758 protein-coding genes in 125.9 Mb of B chromosome sequence, of which at least 88 are expressed. Our results demonstrate that transposable elements in the B chromosome are shared with the standard A chromosome set but multiple lines of evidence fail to detect a syntenic genic region in the A chromosomes, suggesting a distant origin. The current gene content is a result of continuous transfer from the A chromosomal complement over an extended evolutionary time with subsequent degradation but with selection for maintenance of this nonvital chromosome.


Asunto(s)
Cromosomas de las Plantas/genética , Evolución Molecular , Polen/genética , Proteínas Gestacionales/genética , Zea mays/genética , Meiosis/genética , Mitosis/genética
14.
Clin Biomech (Bristol, Avon) ; 87: 105411, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34144390

RESUMEN

BACKGROUND: A calcar collar may reduce risk of periprosthetic fracture of the femur, through collar contact. We estimated the effect of collar contact on periprosthetic fracture mechanics using a collared fully coated cementless femoral stem and then estimated the effect of initial calcar-collar separation on the likelihood of collar contact. METHODS: Three groups of six composite left femurs with increasing calcar-collar separation in each group, underwent periprosthetic fracture simulation in a materials testing machine. Fracture torque and rotational displacement were measured and torsional stiffness and rotational work prior to fracture were estimated. Calcar collar contact prior to fracture was identified using high speed camera footage. FINDINGS: Where calcar-collar contact occurred fracture torque was greater (47.33 [41.03 to 50.45] Nm versus 38.26 [33.70 to 43.60] Nm, p = 0.05), Rotational displacement was less (16.6 [15.5 to 22.3] degrees versus 21.2 [18.9 to 28.1] degrees, p = 0.07), torsional stiffness was greater (151.38 [123.04 to 160.42] rad.Nm-1 versus 96.86 [84.65 to 112.98] rad.Nm-1, p < 0.01) and rotational work was similar (5.88 [4.67, 6.90] J versus 5.31 [4.40, 6.56] J, p = 0.6). Odds ratio (OR) of not achieving collar contact (95% confidence interval) increased 3.8 fold (95% CI 1.6 to 30.2, p < 0.05) for each millimetre of separation in the regression model. 95% chance of collar contact was associated with a separation of 1 mm or less. INTERPRETATION: Surgeons should reduce calcar-collar separation at stem implantation to a maximum of 1 mm to increase the chance of calcar-collar contact during injury and reduce the risk of early post-operative femoral fracture.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Fémur , Prótesis de Cadera , Fracturas Periprotésicas , Artroplastia de Reemplazo de Cadera/efectos adversos , Fracturas del Fémur/etiología , Fracturas del Fémur/cirugía , Fémur/diagnóstico por imagen , Fémur/cirugía , Humanos , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía
15.
Clin Sci (Lond) ; 135(7): 865-884, 2021 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-33769466

RESUMEN

Biliary atresia (BA) is an immune-related disorder and signal transducer and activator of transcription 3 (STAT3) is a key signalling molecule in inflammation. The present study was designed to clarify the function of STAT3 in BA. STAT3 expression was examined in patients and a mouse BA model in which STAT3 levels were further altered with a specific inhibitor or activator. Neutrophil accumulation and the levels of the neutrophil chemoattractants (C-X-C motif) ligand 1 (CXCL1) and IL-8 were determined. The effects of STAT3 inhibition on IL-8 expression were examined in human biliary epithelial cell (BEC) cultures. Functional changes in liver STAT3+ neutrophils in the mouse model were analysed with 10× single cell RNA-seq methods. Results showed STAT3 and p-STAT3 expression was reduced in BA liver tissue compared with control samples. Administration of a STAT3 inhibitor increased jaundice and mortality and reduced body weight in BA mice. In contrast, the STAT3 activator ameliorated BA symptoms. Extensive neutrophil accumulation together with CXCL1 up-regulation, both of which were suppressed by an anti-CXCL1 antibody, were observed in the STAT3 inhibitor-treated group. Recombinant IL-8 administration increased disease severity in BA mice, and the STAT3 activator had the reverse effect. Inhibiting STAT3 increased apoptosis of human BECs together with up-regulated IL-8 expression. RNA-seq analysis revealed reduced the numbers of STAT3 expressing neutrophil in BA which was accompanied by marked enhanced interferon-related antiviral activities. In conclusion, STAT3 reduction, enhanced IL-8 and CXCL1 expression and promoted the accumulation of interferon-responsive neutrophils resulting in BEC damage in BA.


Asunto(s)
Atresia Biliar/patología , Quimiocina CXCL1/metabolismo , Interleucina-8/metabolismo , Infiltración Neutrófila , Factor de Transcripción STAT3/metabolismo , Animales , Atresia Biliar/metabolismo , Quimiocina CXCL1/genética , Modelos Animales de Enfermedad , Células Epiteliales , Humanos , Lactante , Hígado/metabolismo , Ratones Endogámicos BALB C , Rotavirus , Infecciones por Rotavirus , Factor de Transcripción STAT3/genética
16.
Nat Plants ; 7(1): 34-41, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33398155

RESUMEN

Although plants are able to withstand a range of environmental conditions, spikes in ambient temperature can impact plant fertility causing reductions in seed yield and notable economic losses1,2. Therefore, understanding the precise molecular mechanisms that underpin plant fertility under environmental constraints is critical to safeguarding future food production3. Here, we identified two Argonaute-like proteins whose activities are required to sustain male fertility in maize plants under high temperatures. We found that MALE-ASSOCIATED ARGONAUTE-1 and -2 associate with temperature-induced phased secondary small RNAs in pre-meiotic anthers and are essential to controlling the activity of retrotransposons in male meiocyte initials. Biochemical and structural analyses revealed how male-associated Argonaute activity and its interaction with retrotransposon RNA targets is modulated through the dynamic phosphorylation of a set of highly conserved, surface-located serine residues. Our results demonstrate that an Argonaute-dependent, RNA-guided surveillance mechanism is critical in plants to sustain male fertility under environmentally constrained conditions, by controlling the mutagenic activity of transposons in male germ cells.


Asunto(s)
Elementos Transponibles de ADN/genética , Zea mays/genética , Producción de Cultivos , Elementos Transponibles de ADN/fisiología , Fertilidad , Respuesta al Choque Térmico , Plantas Modificadas Genéticamente , Polen/crecimiento & desarrollo , Polen/fisiología , Proteómica , Zea mays/crecimiento & desarrollo , Zea mays/fisiología
17.
Hip Int ; 31(5): 609-617, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32750263

RESUMEN

INTRODUCTION: The angle of acetabular (cup) radiographic inclination is an important measurement in total hip arthroplasty (THA) procedures. Abnormal radiographic inclination is associated with dislocation, edge loading and higher failure rates. Consistently achieving a satisfactory radiographic inclination remains a challenge. Inclinometers have been increasingly used over the last decade. This paper reviews the literature to determine whether using an inclinometer improves the accuracy of acetabular cup inclination in THA. METHODS: A systematic literature search was performed. The following search terms were used: ('hip' OR 'hip replacement' OR 'hip arthroplasty' OR 'primary hip replacement' OR 'THR' OR 'THA' OR 'Acetabular cup Inclination') AND ('Inclinometer'). Titles and abstracts were screened for relevance. Both radiographic and operative inclination comparisons were included. RESULTS: 7 studies met the inclusion criteria. 2 were randomised control trials with level I evidence, and the remaining studies were cohort studies with level III/IV evidence. 5 were clinical and 2 experimental. In total there were 16 cohorts: 7 using an inclinometer, 6 freehand, and 3 using MAG techniques. All studies comparing radiographic inclination and 1 of 2 studies comparing operative inclination showed an improvement in the attainment of the optimal inclination. Similarly, the use of an inclinometer showed a reduction in the number of outliers when compared to MAG and freehand techniques. DISCUSSION: This review demonstrates that using an inclinometer improved the surgeon's ability to achieve their intended inclination (both operative and radiographic) and reduced the incidence of positioning outside the safe-zone. However, only 2 of the studies were randomised control trials and these resulted in opposing conclusions. Therefore, further studies looking at the use of inclinometers would prove useful in understanding their true benefit.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Humanos
18.
EFORT Open Rev ; 5(9): 558-567, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33072408

RESUMEN

The rising incidence of postoperative periprosthetic femoral fracture (PFF) presents a significant clinical and economic burden.A detailed understanding of risk factors is required in order to guide preventative strategies.Different femoral stems have unique characteristics and management strategies must be tailored appropriately.Consensus regarding treatment of PFFs around well-fixed stems is lacking, but revision surgery may provide more predictable outcomes for unstable fracture patterns and fractures around polished taper-slip stems.Future research should focus on implant-related risk factors, treatment of concurrent metabolic bone disease and the use of large endoprostheses. Cite this article: EFORT Open Rev 2020;5:558-567. DOI: 10.1302/2058-5241.5.200003.

19.
J Surg Educ ; 77(4): 817-829, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32217124

RESUMEN

OBJECTIVE: To assess the quality and duration of trauma and orthopedics (T&O) training in medical schools in United Kingdom (UK), and to evaluate final-year students' self-perceived level of competence in essential T&O skills. DESIGN: This was a survey-based study of final-year medical students that attended 1-day undergraduate T&O courses held between Feb'17 and Feb'19. Outcome measures were duration and perceived quality of undergraduate T&O placements, students' self-rated competence in essential T&O skills, and impact of teaching methods on their subjective future competence. SETTING: Four courses held at education centers in 3 different locations in UK (London, Nottingham, and Leeds) PARTICIPANTS: All 414 course attendees from 13 UK medical schools completed the questionnaire. RESULTS: 19.3% of students had not experienced a placement in T&O. Mean duration of T&O placements was 2.5 weeks. 37.4% described their training as "poor". Majority of students attended 1-5 sessions of: lectures (50.5%), small group teaching (58.7%), trauma meetings (58.7%), clinics (65.7%), and theatres (72.5%). Lowest competency scores were reported in management of T&O emergencies, fracture management, and interpretation of T&O radiographs. Self-rated competence in essential T&O skills was significantly higher in students with previous experience of a T&O placement (p < 0.05). There was a strongly positive correlation between small group teaching attendance and perceived competence in management of T&O patients in different clinical settings (p < 0.001). CONCLUSIONS: Medical schools in UK are currently failing to adequately train medical graduates to manage T&O patients, with students reporting low competency scores in all basic T&O skills. To mitigate the current situation, a minimum duration of a T&O placement for all students must be implemented nationally. Educational boards and medical schools must work in collaboration to improve the delivery of undergraduate T&O curriculum, the structure of the clinical T&O placement, and efficacy of the commonly encountered learning environments.


Asunto(s)
Educación de Pregrado en Medicina , Ortopedia , Estudiantes de Medicina , Competencia Clínica , Curriculum , Humanos , Londres , Encuestas y Cuestionarios , Reino Unido
20.
Bone Joint J ; 101-B(10): 1199-1208, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31564148

RESUMEN

AIMS: We compared implant and patient survival following intraoperative periprosthetic femoral fractures (IOPFFs) during primary total hip arthroplasty (THA) with matched controls. PATIENTS AND METHODS: This retrospective cohort study compared 4831 hips with IOPFF and 48 154 propensity score matched primary THAs without IOPFF implanted between 2004 and 2016, which had been recorded on a national joint registry. Implant and patient survival rates were compared between groups using Cox regression. RESULTS: Ten-year stem survival was worse in the IOPFF group (p < 0.001). Risk of revision for aseptic loosening increased 7.2-fold following shaft fracture and almost 2.8-fold after trochanteric fracture (p < 0.001). Risk of periprosthetic fracture of the femur revision increased 4.3-fold following calcar-crack and 3.6-fold after trochanteric fracture (p < 0.01). Risk of instability revision was 3.6-fold after trochanteric fracture and 2.4-fold after calcar crack (p < 0.001). Risk of 90-day mortality following IOPFF without revision was 1.7-fold and 4.0-fold after IOPFF with early revision surgery versus uncomplicated THA (p < 0.001). CONCLUSION: IOPFF increases risk of stem revision and mortality up to ten years following surgery. The risk of revision depends on IOPFF subtype and mortality risk increases with subsequent revision surgery. Surgeons should carefully diagnose and treat IOPFF to minimize fracture progression and implant failure. Cite this article: Bone Joint J 2019;101-B:1199-1208.


Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Osteoartritis de la Cadera/cirugía , Fracturas Periprotésicas/cirugía , Sistema de Registros , Reoperación/métodos , Factores de Edad , Anciano , Artroplastia de Reemplazo de Cadera/métodos , Estudios de Casos y Controles , Inglaterra , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Irlanda del Norte , Osteoartritis de la Cadera/diagnóstico por imagen , Fracturas Periprotésicas/diagnóstico por imagen , Fracturas Periprotésicas/epidemiología , Modelos de Riesgos Proporcionales , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Gales
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