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1.
Nature ; 588(7836): E1, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33188369

RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Nature ; 555(7698): 647-651, 2018 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-29562229

RESUMEN

Periodic food shortages are a major challenge faced by organisms in natural habitats. Cave-dwelling animals must withstand long periods of nutrient deprivation, as-in the absence of photosynthesis-caves depend on external energy sources such as seasonal floods. Here we show that cave-adapted populations of the Mexican tetra, Astyanax mexicanus, have dysregulated blood glucose homeostasis and are insulin-resistant compared to river-adapted populations. We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia. Hybrid fish from surface-cave crosses carrying this mutation weigh more than non-carriers, and zebrafish genetically engineered to carry the mutation have increased body weight and insulin resistance. Higher body weight may be advantageous in caves as a strategy to cope with an infrequent food supply. In humans, the identical mutation in the insulin receptor leads to a severe form of insulin resistance and reduced lifespan. However, cavefish have a similar lifespan to surface fish and do not accumulate the advanced glycation end-products in the blood that are typically associated with the progression of diabetes-associated pathologies. Our findings suggest that diminished insulin signalling is beneficial in a nutrient-limited environment and that cavefish may have acquired compensatory mechanisms that enable them to circumvent the typical negative effects associated with failure to regulate blood glucose levels.


Asunto(s)
Aclimatación/fisiología , Ecosistema , Conducta Alimentaria , Peces/fisiología , Resistencia a la Insulina , Inanición , Envejecimiento/sangre , Envejecimiento/fisiología , Animales , Glucemia/metabolismo , Peso Corporal/genética , Cuevas , Femenino , Peces/sangre , Productos Finales de Glicación Avanzada/sangre , Homeostasis , Insulina/metabolismo , Masculino , Mutación , Receptor de Insulina/genética , Receptor de Insulina/metabolismo
3.
Eur J Orthop Surg Traumatol ; 34(2): 1173-1181, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37989870

RESUMEN

PURPOSE: To determine if incisional negative pressure wound therapy is protective against post-operative surgical site complications following definitive fixation of bicondylar tibial plateau fractures. METHODS: A retrospective analysis of patients diagnosed with an acute bicondylar tibial plateau fracture (AO/OTA 41-C) undergoing ORIF from 2010 to 2020 was performed. Patients received either a standard sterile dressing (SD) or incisional negative pressure wound therapy (iNPWT). Primary outcomes included surgical site infection, osteomyelitis, and wound dehiscence. Secondary outcomes included non-union and return to the operating room. Multivariate logistic regression analyses were performed. RESULTS: 180 patients were included and 22% received iNPWT (n = 40) and 78% received standard dressings (n = 140). iNPWT was more common in active smokers (24.7% vs. 19.3%, p = 0.002) and the SD group was more likely to be lost to follow up (3.6% vs. 0%, p = 0.025). iNPWT was not protective against infection or surgical site complications, and in fact, was associated with higher odds of post-operative infection (OR: 8.96, p = 0.005) and surgical site complications (OR:4.874, p = 0.009) overall. Alcohol abuse (OR: 19, p = 0.005), tobacco use (OR: 4.67, p = 0.009), and time to definitive surgery (OR = 1.21, p = 0.033) were all independent risk factors for post-operative infection. CONCLUSION: In this series of operatively treated bicondylar tibial plateau fractures, iNPWT did not protect against post-operative surgical site complications compared to conventional dressings. Tobacco use, alcohol abuse, and time to definitive surgery, were independent risk factors for post-operative infection. Further studies are needed to determine if iNPWT offers a protective benefit in exclusively high-risk patients with relevant medical and social history.


Asunto(s)
Alcoholismo , Terapia de Presión Negativa para Heridas , Fracturas de la Tibia , Fracturas de la Meseta Tibial , Humanos , Estudios Retrospectivos , Alcoholismo/etiología , Fracturas de la Tibia/cirugía , Fracturas de la Tibia/etiología , Fijación Interna de Fracturas/efectos adversos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control
4.
Eur J Orthop Surg Traumatol ; 34(3): 1675-1681, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38403660

RESUMEN

PURPOSE: To determine outcomes following surgical management of terrible triad injuries in patients treated with and without a hinged elbow orthosis (HEO) in the post-operative setting. METHODS: This study was a retrospective review of 41 patients who underwent surgical treatment of terrible triad injuries including radial head fracture, coronoid fracture, and ulnohumeral dislocation between 2008 and 2023 with at least 10-week follow-up. RESULTS: Nineteen patients were treated post-operatively without HEO, and 22 patients were treated with HEO. There were no differences in range of motion (ROM) between patients treated with and without HEO in final flexion-extension arc (118.4° no HEO, 114.6° HEO, p = 0.59) or pronation-supination arc (147.8° no HEO, 141.4° HEO, p = 0.27). Five patients treated without HEO and one patient treated with HEO returned to the operating room for stiffness (26%, 5%, p = 0.08). QuickDASH scores were similar between groups (p = 0.69). CONCLUSIONS: This study found no difference in post-operative ROM, complications, or QuickDASH scores in patients treated post-operatively with or without HEO. Based on these results, we cannot determine whether the use of HEO adds additional stability to the elbow while initiating ROM exercises post-operatively.


Asunto(s)
Lesiones de Codo , Articulación del Codo , Luxaciones Articulares , Inestabilidad de la Articulación , Fracturas del Radio , Humanos , Codo , Inestabilidad de la Articulación/etiología , Resultado del Tratamiento , Articulación del Codo/cirugía , Luxaciones Articulares/etiología , Luxaciones Articulares/cirugía , Fracturas del Radio/cirugía , Fracturas del Radio/etiología , Aparatos Ortopédicos , Rango del Movimiento Articular , Estudios Retrospectivos , Fijación Interna de Fracturas/efectos adversos
5.
Adm Soc ; 55(3): 351-380, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38603325

RESUMEN

This study relies on a cultural theory of risk to examine how cultural biases (hierarchy, individualism, egalitarianism, and fatalism) of local government officials affect their COVID-19 risk perception and support for COVID-19 mitigation measures. After controlling for partisanship, religiosity, and other factors, the analysis of survey data from county governments in the U.S. revealed that cultural biases matter. Officials with egalitarian and hierarchical cultural biases report higher support for adopting COVID-19 mitigation measures, while those with individualistic cultural biases report lower support. These findings highlight the need to understand cultural worldviews and develop cultural competencies necessary for governing traumatic events.

6.
Angew Chem Int Ed Engl ; 62(16): e202218911, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-36760211

RESUMEN

The use of thermally activated delayed fluorescence (TADF) emitters and emitters that show preferential horizontal orientation of their transition dipole moment (TDM) are two emerging strategies to enhance the efficiency of OLEDs. We present the first example of a liquid crystalline multi-resonance TADF (MR-TADF) emitter, DiKTa-LC. The compound possesses a nematic liquid crystalline phase between 80 °C and 110 °C. Importantly, the TDM of the spin-coated film shows preferential horizontal orientation, with an anisotropy factor, a, of 0.28, which is preserved in doped poly(vinylcarbazole) films. Green-emitting (λEL =492 nm) solution-processed OLEDs based on DiKTa-LC showed an EQEmax of 13.6 %. We thus demonstrate for the first time how self-assembly of a liquid crystalline TADF emitter can lead to the so-far elusive control of the orientation of the transition dipole in solution-processed films, which will be of relevance for high-performance solution-processed OLEDs.

7.
Eur J Orthop Surg Traumatol ; 33(5): 1629-1633, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35788424

RESUMEN

OBJECTIVE: To determine if screw fixation across a cement mantle is safe and effective during plate fixation of well-fixed periprosthetic femur fractures. DESIGN: Retrospective cohort study. SETTING: Academic Level I Trauma Center. PATIENTS: Twenty-eight patients with AO/OTA 32A[B1] or 32A[C] periprosthetic femur fractures treated with open reduction and internal plate and screw fixation after cemented or uncemented hip arthroplasty. INTERVENTION: Screw placement into the cement mantle during internal fixation. OUTCOME MEASUREMENTS: Primary outcome was revision arthroplasty for aseptic loosening. Secondary outcomes included radiographic evidence of aseptic loosening, infection, nonunion, implant failure, and overall reoperation rate. RESULTS: There were 28 patients who met inclusion criteria. A total of 9 patients had screws placed in the cement mantle while the remaining 19 patients had screws placed around an uncemented stem. At a mean of 3.7-year follow-up, there were no cases of revision arthroplasty or aseptic loosening in either group. There were no significant differences in rates of infection, nonunion, implant failure, or reoperation rate between patients who had screw placement into a cement mantle vs around an uncemented stem. CONCLUSION: Drilling into the cement mantle during fixation of a periprosthetic femur fracture around a well-fixed cemented hip stem appears safe and effective. When possible, surgeons can consider bicortical screws around a cemented stem, given the biomechanical advantages over unicortical screw or cerclage fixation. Larger prospective trials confirming the safety of this technique are warranted prior to routine implementation. LEVEL OF EVIDENCE: III.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Fracturas del Fémur , Prótesis de Cadera , Fracturas Periprotésicas , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Prótesis de Cadera/efectos adversos , Estudios Prospectivos , Estudios Retrospectivos , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Reoperación/efectos adversos , Fracturas del Fémur/etiología , Fracturas del Fémur/cirugía , Cementos para Huesos/efectos adversos , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/métodos , Fémur/cirugía
8.
Chemphyschem ; 23(13): e202200154, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35446455

RESUMEN

Two series of flavylium triflates carrying alkoxy side chains in the A-ring (benzo unit of chromylium salt) and thioethers in the B ring (phenyl unit) (On -Fla-Sm ) as well as thioethers at both A and B ring (Sn -Fla-Sm ) were synthesized in order to understand the effect of thioether functionalization on their self-assembly and electronic properties. Concentration-dependent and diffusion ordered (DOSY) NMR experiments of O1 -iV-Fla-S3 indicate the formation of columnar H-aggregates in solution with antiparallel intracolumnar stacking of the AC unit (chromylium) of the flavylium triflate, in agreement with the solid state structure of O1 -V-Fla-S1 . Thioether substitution on the B ring changes the linear optical properties in solution, whereas it has no effect on the A ring. According to differential scanning calorimetry, polarizing optical microscopy and X-ray diffraction bulk self-assembly of these ionic liquid crystals (ILCs) depends on the total number of side chains, yielding SmA and LamCol phases for ILCs with 2-3 chains and Colro , Colh phases for ILCs with 3-6 chains. Thus, we demonstrated that thioethers are a useful design tool for ILCs with tailored properties.


Asunto(s)
Líquidos Iónicos , Cristales Líquidos , Rastreo Diferencial de Calorimetría , Líquidos Iónicos/química , Cristales Líquidos/química , Sales (Química)/química , Sulfuros , Difracción de Rayos X
9.
Nature ; 531(7592): 105-9, 2016 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-26863197

RESUMEN

The enteric nervous system (ENS) is the largest component of the autonomic nervous system, with neuron numbers surpassing those present in the spinal cord. The ENS has been called the 'second brain' given its autonomy, remarkable neurotransmitter diversity and complex cytoarchitecture. Defects in ENS development are responsible for many human disorders including Hirschsprung disease (HSCR). HSCR is caused by the developmental failure of ENS progenitors to migrate into the gastrointestinal tract, particularly the distal colon. Human ENS development remains poorly understood owing to the lack of an easily accessible model system. Here we demonstrate the efficient derivation and isolation of ENS progenitors from human pluripotent stem (PS) cells, and their further differentiation into functional enteric neurons. ENS precursors derived in vitro are capable of targeted migration in the developing chick embryo and extensive colonization of the adult mouse colon. The in vivo engraftment and migration of human PS-cell-derived ENS precursors rescue disease-related mortality in HSCR mice (Ednrb(s-l/s-l)), although the mechanism of action remains unclear. Finally, EDNRB-null mutant ENS precursors enable modelling of HSCR-related migration defects, and the identification of pepstatin A as a candidate therapeutic target. Our study establishes the first, to our knowledge, human PS-cell-based platform for the study of human ENS development, and presents cell- and drug-based strategies for the treatment of HSCR.


Asunto(s)
Linaje de la Célula , Tratamiento Basado en Trasplante de Células y Tejidos , Descubrimiento de Drogas/métodos , Sistema Nervioso Entérico/patología , Enfermedad de Hirschsprung/tratamiento farmacológico , Enfermedad de Hirschsprung/patología , Neuronas/patología , Envejecimiento , Animales , Diferenciación Celular , Línea Celular , Movimiento Celular , Separación Celular , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Embrión de Pollo , Colon/efectos de los fármacos , Colon/patología , Modelos Animales de Enfermedad , Femenino , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/patología , Enfermedad de Hirschsprung/terapia , Humanos , Masculino , Ratones , Neuronas/efectos de los fármacos , Pepstatinas/metabolismo , Células Madre Pluripotentes/patología , Receptor de Endotelina B/metabolismo , Transducción de Señal
10.
Arch Orthop Trauma Surg ; 142(7): 1367-1374, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33484311

RESUMEN

OBJECTIVES: The purpose of the study was to compare treatment outcomes after short or long cephalomedullary nailing for intertrochanteric femur fractures. DATA SOURCES: A systematic review of perioperative outcomes after short or long cephalomedullary nailing for intertrochanteric femur fractures was performed. The following databases were used: using the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980-2019), and MEDLINE (1980-2019). The queries were performed in June 2019. STUDY SELECTION: The following search term query was used: "Intramedullary Nail AND Intertrochanteric Fracture OR "Long OR Short Nail AND intertrochanteric Fracture." Studies were excluded if they were "single-arm" studies (i.e., reporting on either long or short CMN but not both), or did not report at least one of the outcomes being meta-analyzed. Furthermore, cadaveric studies, animal studies, basic science articles, editorial articles, surveys and studies were excluded. DATA EXTRACTION: Two investigators independently reviewed abstracts from all identified articles. Full-text articles were obtained for review if necessary, to allow further assessment of inclusion and exclusion criteria. Additionally, all references from the included studies were reviewed and reconciled to verify that no relevant articles were missing from the systematic review. DATA SYNTHESIS: Short nails were associated with statistically significantly less estimated blood loss and operative time compared to long nails. There were no significant differences in transfusion rates, implant failures or overall re-operation rates between implant lengths. Similarly, there was no significant difference in peri-implant fracture between implant lengths. CONCLUSIONS: Overall, the available clinical evidence supports the use of short cephalomedullary nails for the majority of intertrochanteric femur fractures. STUDY DESIGN/LEVEL OF EVIDENCE: Meta-analysis; Level III, therapeutic.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Fracturas Periprotésicas , Clavos Ortopédicos , Fracturas de Cadera/cirugía , Humanos , Estudios Retrospectivos , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
11.
Eur J Orthop Surg Traumatol ; 32(5): 933-938, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34176011

RESUMEN

PURPOSE: Significant time and resources are devoted to conducting orthopaedic biomechanics research; however, it is not known how these studies relate to their subsequent clinical studies. The purpose of the present study was to determine whether biomechanically superior treatments were associated with improved clinical outcomes as determined by analogous randomized controlled trials (RCTs). METHODS: A systematic review was conducted to find RCTs that tested a research question based on a prior biomechanical study. PubMed and SCOPUS databases were queried for orthopaedic randomized controlled trials, and full text articles were reviewed to find RCTs which cited biomechanical studies with analogous comparison groups. A random-effects multi-level logistic regression model was conducted examining the association between RCT outcome and biomechanics outcome, adjusting for multiple outcomes nested within study. RESULTS: In total, 20,261 articles were reviewed yielding 21 RCTs citing a total of 43 analogous biomechanical studies. In 7 instances (16.2%), the RCT and a cited biomechanical study showed concordant results (i.e. the superior treatment in the RCT was also the superior construct in the biomechanical study). RCT outcome was not associated with biomechanical outcome (ß = -1.50, standard error = 0.78, p = .05). CONCLUSION: This study assessed 21 orthopaedic RCTs with 43 corresponding biomechanical studies and found no association between superior biomechanical properties of a given orthopaedic treatment and improved clinical outcomes. Favourable biomechanical properties alone should not be the primary reason for selecting one treatment over another. Furthermore, RCTs based on biomechanical studies should be carefully designed to maximize the chance of providing clinically relevant insights.


Asunto(s)
Ortopedia , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
12.
Eur J Orthop Surg Traumatol ; 32(2): 363-369, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33891154

RESUMEN

PURPOSE: Tranexamic acid (TXA) reduces need for transfusion in total joint arthroplasty, though findings in acetabular surgery are conflicting. We compared outcomes after acetabular fracture surgery with or without perioperative intravenous (IV) TXA administration. METHODS: We performed a retrospective review of 305 patients with acetabular fractures that underwent open reduction and internal fixation (ORIF). Eighty-nine patients received TXA, and 216 did not. The primary outcome was rates of intraoperative and postoperative allogeneic blood transfusion. RESULTS: Baseline demographics and characteristics were similar. Time from injury to surgery and estimated blood loss were comparable. Operative time (p < 0.01) and intraoperative IV fluids (p < 0.01) were greater in the non-TXA group. The proportion of patients who received blood transfusion and mean units transfused intraoperatively and postoperatively did not differ. Mean differences in preoperative and postoperative hemoglobin and hematocrit, hospital length of stay, and perioperative complications also did not differ. In a multivariable regression model, age 60-70 years, Charlson Comorbidity Index, Injury Severity Score, and fracture patterns likely to bleed were independently associated with intraoperative transfusion. Anterior surgical approaches and intraoperative transfusion requirement were independently associated with postoperative transfusion. CONCLUSION: In this study, perioperative IV TXA did not decrease blood loss, need for transfusion, or improve in-hospital outcomes of acetabular fracture surgery. Age 60-70, CCI, ISS, and fracture patterns likely to bleed were independently associated with intraoperative transfusion. Anterior surgical approach and need for intraoperative transfusion were independently associated with postoperative transfusion. Further prospective trials are warranted to confirm these findings.


Asunto(s)
Antifibrinolíticos , Fracturas de Cadera , Ácido Tranexámico , Anciano , Pérdida de Sangre Quirúrgica/prevención & control , Hospitales , Humanos , Persona de Mediana Edad , Estudios Retrospectivos
13.
Appl Environ Microbiol ; 87(18): e0112321, 2021 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-34232062

RESUMEN

Cell chaining in Bacillus subtilis is naturally observed in a subset of cells during exponential growth and during biofilm formation. However, the recently constructed large-scale genome-minimized B. subtilis strain PG10 displays a severe and permanent defect in cell separation, as it exclusively grows in the form of long filaments of nonseparated cells. In this study, we investigated the underlying mechanisms responsible for the incomplete cell division of PG10 by genomic and transcriptomic analyses. Repression of the SigD regulon, including the major autolysin gene lytF, was identified as the cause for the cell separation problem of PG10. It appeared that SigD-regulated genes are downregulated in PG10 due to the absence of the flagellar export apparatus, which normally is responsible for secretion of FlgM, the anti-sigma factor of SigD. Although mild negative effects on growth and cell morphology were observed, deletion of flgM could revert the aberrant cell-chaining phenotype and increased transformation efficiency. Interestingly, our work also demonstrates the occurrence of increased antisense transcription of slrR, a transcriptional repressor of autolysin genes, in PG10 and provides further understanding for this observation. In addition to revealing the molecular basis of the cell separation defect in PG10, our work provides novel targets for subsequent genome reduction efforts and future directions for further optimization of miniBacillus PG10. IMPORTANCE Reduction of the size of bacterial genomes is relevant for understanding the minimal requirements for cellular life as well as from a biotechnological point of view. Although the genome-minimized Bacillus subtilis strain PG10 displays several beneficial traits as a microbial cell factory compared to its parental strain, a defect at the final stage of cell division was introduced during the genome reduction process. By genetic and transcriptomic analyses, we identified the underlying reasons for the cell separation problem of PG10. In addition to enabling PG10 to grow in a way similar to that of B. subtilis wild-type strains, our work points toward subsequent targets for fine-tuning and further reduction of the genome of PG10. Moreover, solving the cell separation defect facilitates laboratory handling of PG10 by increasing the transformation efficiency, among other means. Overall, our work contributes to understanding and improving biotechnologically attractive minimal bacterial cell factories.


Asunto(s)
Bacillus subtilis/citología , Bacillus subtilis/genética , División Celular , N-Acetil Muramoil-L-Alanina Amidasa/genética , Proteínas Bacterianas/genética , Perfilación de la Expresión Génica , Microbiología Industrial
14.
Neurol Sci ; 42(1): 25-33, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33140308

RESUMEN

BACKGROUND: Emerging evidence suggests that a subset of coronavirus disease 2019 (COVID-19) patients may present with or develop cerebrovascular disease during the course of hospitalization. Whereas ischemic stroke in COVID-19 patients has been well described, data on intracranial hemorrhage (ICH) in these patients is still limited. We, therefore, conducted a rapid systematic review of current scientific literature to identify and consolidate evidence of ICH in COVID-19 patients. METHODS: A systematic search of literature was conducted between November 1, 2019, and August 14, 2020, on PubMed and China National Knowledge Infrastructure (CNKI) to identify eligible studies. RESULTS: A total of 23 studies describing ICH in 148 COVID-19 patients were included. The pooled incidence of ICH in COVID-19 patients was 0.7% (95% CI 0.5-0.9), with low levels of inter-study heterogeneity observed (I2 = 33.6%, Cochran's Q = 12.05, p = 0.149). Most of the patients were elderly male patients (65.8%) with comorbidities, the most common being systemic hypertension (54%). Hemorrhage involving multiple cranial compartments was reported in 9.5% of cases. Single compartments were involved in the rest, with intraparenchymal hemorrhage (IPH) being the most common variety (62.6%) and intraventricular hemorrhage (IVH) the least common (1.4%). Half of these patients were on some form of anticoagulation. Overall, the mortality rate in the COVID-19 patients with ICH was about 48.6%. CONCLUSION: Although relatively uncommon among COVID-19 patients, ICH is associated with a high mortality rate. Early identification of patients at risk of developing ICH, particularly with comorbid conditions and on anticoagulant therapy, may be important to improve outcomes.


Asunto(s)
COVID-19/complicaciones , COVID-19/mortalidad , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/mortalidad , Humanos
15.
Proc Natl Acad Sci U S A ; 115(37): E8775-E8782, 2018 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-30154162

RESUMEN

Herpes simplex virus type 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in Western countries. Some HSE children carry inborn errors of the Toll-like receptor 3 (TLR3)-dependent IFN-α/ß- and -λ-inducing pathway. Induced pluripotent stem cell (iPSC)-derived cortical neurons with TLR3 pathway mutations are highly susceptible to HSV-1, due to impairment of cell-intrinsic TLR3-IFN immunity. In contrast, the contribution of cell-intrinsic immunity of human trigeminal ganglion (TG) neurons remains unclear. Here, we describe efficient in vitro derivation and purification of TG neurons from human iPSCs via a cranial placode intermediate. The resulting TG neurons are of sensory identity and exhibit robust responses to heat (capsaicin), cold (icilin), and inflammatory pain (ATP). Unlike control cortical neurons, both control and TLR3-deficient TG neurons were highly susceptible to HSV-1. However, pretreatment of control TG neurons with poly(I:C) induced the cells into an anti-HSV-1 state. Moreover, both control and TLR3-deficient TG neurons developed resistance to HSV-1 following pretreatment with IFN-ß but not IFN-λ. These data indicate that TG neurons are vulnerable to HSV-1 because they require preemptive stimulation of the TLR3 or IFN-α/ß receptors to induce antiviral immunity, whereas cortical neurons possess a TLR3-dependent constitutive resistance that is sufficient to block incoming HSV-1 in the absence of prior antiviral signals. The lack of constitutive resistance in TG neurons in vitro is consistent with their exploitation as a latent virus reservoir in vivo. Our results incriminate deficiencies in the constitutive TLR3-dependent response of cortical neurons in the pathogenesis of HSE.


Asunto(s)
Inmunidad/inmunología , Células Madre Pluripotentes Inducidas/metabolismo , Neuronas/metabolismo , Receptor Toll-Like 3/metabolismo , Antivirales/farmacología , Diferenciación Celular/genética , Células Cultivadas , Corteza Cerebral/citología , Niño , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 1/fisiología , Humanos , Inmunidad/genética , Células Madre Pluripotentes Inducidas/citología , Interferón beta/farmacología , Mutación , Neuronas/efectos de los fármacos , Neuronas/virología , Poli I-C/farmacología , Receptor Toll-Like 3/genética , Ganglio del Trigémino/citología
16.
Instr Course Lect ; 70: 563-576, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33438936

RESUMEN

The practicing orthopaedic surgeon must understand the relationship between fracture biomechanics and fracture biology to optimize patient outcomes. Patient characteristics, fracture pattern, and desired type of bone healing all drive decision making. The benefits of performing an open approach to a fracture, obtaining an anatomic reduction, and achieving absolute stability must be weighed against the biologic cost to the tissues and the potential to compromise healing. Similarly, the decision to perform a closed fracture reduction; apply a splint, bridge plate, or intramedullary nail; and achieve relative stability requires that the surgeon understand the implications of increased strain at a given fracture site. The purpose of this chapter is to review the basic science of primary and secondary bone healing with special attention given to the clinical implications for practicing surgeons.


Asunto(s)
Fijación Intramedular de Fracturas , Ortopedia , Biofisica , Clavos Ortopédicos , Curación de Fractura , Humanos
17.
Eur J Orthop Surg Traumatol ; 31(3): 473-479, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32949271

RESUMEN

BACKGROUND: The need for coracoclavicular (CC) ligament augmentation when performing locking plate fixation of unstable distal clavicle fractures is controversial. The purpose of this study was to compare the results after locking plate fixation for treatment of Neer type-II and type-V distal clavicle fractures with and without suture suspensory augmentation of the CC ligaments. METHODS: This was a retrospective case series of all Neer type-II and type-V distal clavicle fractures treated with locking plates at a single Level I trauma center. Patients were separated into locking plate-only and locking plate with CC ligament augmentation groups. Postoperative complications and fracture healing rates were recorded. Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores were recorded as functional outcomes during follow-up phone interviews. Standard descriptive statistics were performed. RESULTS: Sixteen patients were treated with locking plate fixation-only, and seven patients were treated with additional CC ligament augmentation. There was a similar distribution of Neer fracture types with each group. All fractures in both groups went onto union without loss of reduction or implant failure. There were no cases of infection or wound complications in either group. QuickDASH scores were comparable between locking plate-only fixation (mean 4.1 ± 3.9) and additional suspensory suture fixation (mean 4.5 ± 3.6). CONCLUSION: This comparative study of Neer type-II and type-V distal clavicle fractures demonstrated comparable outcomes after locking plate fixation with and without CC ligament augmentation. CC ligament augmentation may not be necessary when treating unstable distal clavicle fractures if locking plate fixation is used.


Asunto(s)
Clavícula , Fracturas Óseas , Placas Óseas , Clavícula/cirugía , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Humanos , Ligamentos Articulares/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
18.
Eur J Orthop Surg Traumatol ; 31(7): 1529-1534, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33575843

RESUMEN

Here we describe the surgical technique for using distal femoral fine wire traction during retrograde femoral nailing and present case examples. This technique allows for hands-free distraction across the fracture site to restore length and alignment, while not interfering with the preparation and insertion of the retrograde femoral nail. Distal femoral fine wire traction is a useful adjunctive technique to restore length and effect an indirect reduction in femur fractures being stabilized with a retrograde nail.


Asunto(s)
Fracturas del Fémur , Fijación Intramedular de Fracturas , Clavos Ortopédicos , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Fémur/diagnóstico por imagen , Fémur/cirugía , Humanos , Tracción
19.
Eur J Orthop Surg Traumatol ; 31(1): 65-70, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32710126

RESUMEN

PURPOSE: The optimal management of valgus-impacted femoral neck fractures remains controversial. Internal fixation is associated with significant rates of re-operation, while historical non-operative management strategies consisting of prolonged bed rest also resulted in patient morbidity. Our hypothesis was that screw fixation would have comparable failure rates to non-operative treatment and immediate mobilization for valgus-impacted femoral neck fractures. METHODS: Retrospective cohort at a single academic Level I trauma center of patients with valgus-impacted femoral neck fractures (AO/OTA 31-B1) treated with percutaneous screw fixation (n = 97) or non-operatively (n = 28). Operative treatment consisted of percutaneous screw fixation. Non-operative treatment consisted of early mobilization. The primary outcome was a salvage operation. Patient demographics were assessed between groups. RESULTS: More non-operatively treated patients were permitted unrestricted weight-bearing (WBAT; p = 0.002). There was no increase in complication rates or mortality, and return to previous ambulatory status was comparable between operatively and non-operatively treated patients. 35.7% (10/28) of non-operatively treated patients underwent a subsequent operation, compared to 15.5% (15/97) of patients with screw fixation (p = 0.03). Only WBAT was independently associated with treatment failure (OR 3.1, 95%CI 1.2-8.3, p =0.02). WBAT was predictive of treatment failure only in the non-operatively treated group (64.3%, 9/14 WBAT vs 8.3%, 1/12 partial, p =0.005). CONCLUSION: After controlling for weight-bearing restrictions, we found no difference in failure rates between non-operative treatment and screw fixation. Non-operative treatment with partial weight-bearing had low failure rates, comparable complication and mortality rates, and equivalent functional outcomes to operative treatment and is reasonable if a patient would like to avoid surgery and accepts the risk of subsequent arthroplasty. Overall, there were relatively high failure rates in all groups.


Asunto(s)
Tratamiento Conservador , Fracturas del Cuello Femoral , Fijación Interna de Fracturas , Adulto , Anciano , Anciano de 80 o más Años , Tornillos Óseos , Femenino , Fracturas del Cuello Femoral/cirugía , Fracturas del Cuello Femoral/terapia , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento , Soporte de Peso
20.
Eur J Orthop Surg Traumatol ; 31(2): 259-264, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32804288

RESUMEN

Intra-articular screw cut-out is a potential complication of intertrochanteric femur fracture fixation with a cephalomedullary nail. Cement augmentation of fixation in the proximal segment offers the prospect of increased stability and fewer complications, but clinical experience with non-resorbable cement is limited. To determine the handling properties and efficacy of this new technique, we performed a retrospective propensity-matched cohort of forty-four geriatric intertrochanteric femur fractures treated with a cephalomedullary nail with (n = 11) or without (n = 33) augmentation with non-resorbable cement injected into the proximal segment. In the patients treated with cement augmentation, at minimum 3-month follow-up, there were no instances of intra-articular cut-out, and no increase in re-operation compared to conventional fixation. Cement augmentation appears to be safe and effective in geriatric intertrochanteric femur fractures to mitigate risk of cut-out.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Anciano , Cementos para Huesos/uso terapéutico , Clavos Ortopédicos , Fémur/diagnóstico por imagen , Fémur/cirugía , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Humanos , Estudios Retrospectivos
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