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1.
Theor Appl Genet ; 137(5): 107, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632129

RESUMO

In soybean [Glycine max (L.) Merr.], drought stress is the leading cause of yield loss from abiotic stress in rain-fed US growing areas. Only 10% of the US soybean production is irrigated; therefore, plants must possess physiological mechanisms to tolerate drought stress. Slow canopy wilting is a physiological trait that is observed in a few exotic plant introductions (PIs) and may lead to yield improvement under drought stress. Canopy wilting of 130 recombinant inbred lines (RILs) derived from Hutcheson × PI 471938 grown under drought stress was visually evaluated and genotyped with the SoySNP6K BeadChip. Over four years, field evaluations of canopy wilting were conducted under rainfed conditions at three locations across the US (Georgia, Kansas, and North Carolina). Due to the variation in weather among locations and years, the phenotypic data were collected from seven environments. Substantial variation in canopy wilting was observed among the genotypes in the RIL population across environments. Three QTLs were identified for canopy wilting from the RIL population using composite interval mapping on chromosomes (Chrs) 2, 8, and 9 based on combined environmental analyses. These QTLs inherited the favorable alleles from PI 471938 and accounted for 11, 10, and 14% of phenotypic variation, respectively. A list of 106 candidate genes were narrowed down for these three QTLs based on the published information. The QTLs identified through this research can be used as targets for further investigation to understand the mechanisms of slow canopy wilting. These QTLs could be deployed to improve drought tolerance through a targeted selection of the genomic regions from PI 471938.


Assuntos
Glycine max , Locos de Características Quantitativas , Mapeamento Cromossômico , Fenótipo , Genótipo , Secas
2.
JAMA Netw Open ; 7(1): e2351308, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38236603

RESUMO

Importance: Unstable ankle fractures are routinely managed operatively. However, because of soft tissue and implant-related complications, recent literature has reported on the nonoperative management of well-reduced medial malleolus fractures after fibular stabilization, but with limited evidence supporting the routine application. Objective: To assess the superiority of internal fixation of well-reduced (displacement ≤2 mm) medial malleolus fractures compared with nonfixation after fibular stabilization. Design, Setting, and Participants: This superiority, pragmatic, parallel, prospective randomized clinical trial was conducted from October 1, 2017, to August 31, 2021. A total of 154 adult participants (≥16 years) with a closed, unstable bimalleolar or trimalleolar ankle fracture requiring surgery at an academic major trauma center in the UK were assessed. Exclusion criteria included injuries with no medial-sided fracture, open fractures, neurovascular injury, and the inability to comply with follow-up. Data analysis was performed in July 2022 and confirmed in September 2023. Interventions: Once the lateral (and where appropriate, posterior) malleolus had been fixed and satisfactory intraoperative reduction of the medial malleolus fracture was confirmed by the operating surgeon, participants were randomly allocated to fixation (n = 78) or nonfixation (n = 76) of the medial malleolus. Main Outcome and Measure: Olerud-Molander Ankle Score (OMAS) 1 year after randomization (range, 0-100 points, with 0 indicating worst possible outcome and 100 indicating best possible outcome). Results: Among 154 randomized participants (mean [SD] age, 56.5 [16.7] years; 119 [77%] female), 144 (94%) completed the trial. At 1 year, the median OMAS was 80.0 (IQR, 60.0-90.0) in the fixation group compared with 72.5 (IQR, 55.0-90.0) in the nonfixation group (P = .17). Complication rates were comparable. Significantly more patients in the nonfixation group developed a radiographic nonunion (20% vs 0%; P < .001), with 8 of 13 clinically asymptomatic; 1 patient required surgical reintervention for this. Fracture type and reduction quality appeared to influence fracture union and patient outcome. Conclusions and Relevance: In this randomized clinical trial comparing internal fixation of well-reduced medial malleolus fractures with nonfixation, after fibular stabilization, fixation was not superior according to the primary outcome. However, 1 in 5 patients developed a radiographic nonunion after nonfixation, and although the reintervention rate to manage this was low, the future implications are unknown. These results support selective nonfixation of anatomically reduced medial malleolar fractures after fibular stabilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03362229.


Assuntos
Fraturas do Tornozelo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas do Tornozelo/cirurgia , Fraturas do Tornozelo/terapia , Análise de Dados , Fixação Interna de Fraturas , Complicações Pós-Operatórias , Estudos Prospectivos , Idoso
3.
Eur J Orthop Surg Traumatol ; 34(2): 909-918, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37773419

RESUMO

PURPOSE: To determine the feasibility and reliability of ultrasound in the assessment of humeral shaft fracture healing and estimate the accuracy of 6wk ultrasound in predicting nonunion. METHODS: Twelve adults with a non-operatively managed humeral shaft fracture were prospectively recruited and underwent ultrasound scanning at 6wks and 12wks post-injury. Seven blinded observers evaluated sonographic callus appearance to determine intra- and inter-observer reliability. Nonunion prediction accuracy was estimated by comparing images for patients that united (n = 10/12) with those that developed a nonunion (n = 2/12). RESULTS: The mean scan duration was 8 min (5-12) and all patients tolerated the procedure. At 6wks and 12wks, sonographic callus (SC) was present in 11 patients (10 united, one nonunion) and sonographic bridging callus (SBC) in seven (all united). Ultrasound had substantial intra- (weighted kappa: 6wk 0.75; 12wk 0.75) and inter-observer reliability (intraclass correlation coefficient: 6wk 0.60; 12wk 0.76). At 6wks, the absence of SC demonstrated sensitivity 50%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91% in nonunion prediction (overall accuracy 92%). The absence of SBC demonstrated sensitivity 100%, specificity 70%, PPV 40% and NPV 100% in nonunion prediction (overall accuracy 75%). Of three patients at risk of nonunion (Radiographic Union Score for HUmeral fractures < 8), one had SBC on 6wk ultrasound (that subsequently united) and the others had non-bridging/absent SC (both developed nonunion). CONCLUSIONS: Ultrasound assessment of humeral shaft fracture healing was feasible, reliable and may predict nonunion. Ultrasound could be useful in defining nonunion risk among patients with reduced radiographic callus formation.


Assuntos
Fraturas não Consolidadas , Fraturas do Úmero , Adulto , Humanos , Consolidação da Fratura , Fraturas não Consolidadas/diagnóstico por imagem , Fraturas não Consolidadas/etiologia , Fraturas não Consolidadas/cirurgia , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Estudos de Viabilidade , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Úmero , Estudos Retrospectivos , Resultado do Tratamento
4.
Instr Course Lect ; 73: 795-811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38090941

RESUMO

Lateral patellar instability is one of the most common knee disorders among adolescents. Numerous anthropometric features, including trochlear dysplasia, patella alta, high tibial tubercle-to-trochlear groove distance, and coronal and rotational plane malalignment, are considered primary risk factors for patellar dislocation, and the understanding of their complex interplay is continuously evolving. Because of the multifactorial nature of patellar instability, there is a lack of consensus regarding many aspects of surgical intervention. Medial patellofemoral ligament reconstruction is considered to be the essential procedure in preventing recurrent instability. However, there is growing interest in addressing underlying anatomic risk factors that contribute to patellar instability. It is important to discuss the diagnosis and management of patellar instability, surgical considerations in medial patellofemoral ligament reconstruction, mitigation/correction of anatomic risk factors, and treatment of associated chondral lesions.


Assuntos
Instabilidade Articular , Luxação Patelar , Articulação Patelofemoral , Adolescente , Humanos , Articulação Patelofemoral/diagnóstico por imagem , Articulação Patelofemoral/cirurgia , Instabilidade Articular/diagnóstico , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Luxação Patelar/diagnóstico , Luxação Patelar/cirurgia , Articulação do Joelho/cirurgia , Ligamentos Articulares/cirurgia , Tíbia/cirurgia , Patela
5.
Pain Res Manag ; 2023: 6603625, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051562

RESUMO

Introduction: Due to the COVID-19 pandemic, healthcare centers quickly adapted services into virtual formats. Pain clinics in Canada play a vital role in helping people living with pain, and these clinics remained essential services for patients throughout the pandemic. This study aimed to (1) describe and compare the transition from in-person to virtual pain care services at Canadian pain clinics during the onset of the COVID-19 pandemic and (2) provide postpandemic recommendations for pain care services to optimize the quality of patient care. Materials and Methods: We used a qualitative participatory action study design that included a cross-sectional survey for data collection and descriptive analysis to summarize the findings. Survey responses were collected between January and March of 2021. The survey was administered to the leadership teams of 11 adult pain clinics affiliated with the Chronic Pain Centre of Excellence for Canadian Veterans. Responses were analyzed qualitatively to describe the transition to the virtual pain services at pain clinics. Results: We achieved a 100% response rate from participating clinics. The results focus on describing the transition to the virtual care, current treatment and services, the quality of care, program sustainability, barriers to maintaining virtual services, and future considerations. Conclusions: Participating clinics were capable of transitioning pain care services to the virtual formats and have in-person care when needed with proper safety precautions. The pandemic demonstrated that it is feasible and sustainable for pain clinics to have a hybrid of virtual and in-person care to treat those living with pain. It is recommended that moving forward, there should be a hybrid of both virtual and in-person care for pain clinics. Ministries of Health should continue to develop policies and funding mechanisms that support innovations aimed at holistic healthcare, interdisciplinary teams, and the expansion of clinics' geographical reach for patient access.


Assuntos
COVID-19 , Clínicas de Dor , Adulto , Humanos , Estudos Transversais , Pandemias , Canadá , Dor
6.
Curr Rev Musculoskelet Med ; 16(5): 163-172, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37014608

RESUMO

PURPOSE OF REVIEW: Meniscal allograft transplantation is intended to address painful knees with symptoms that can be attributed to meniscal deficiency through injury or meniscectomy. Initially viewed as an experimental procedure, refinements in patient selection and surgical technique have led to improved clinical outcomes with wider acceptance. Our intention with this paper is to provide a review of meniscal allograft transplantation, with the focus on the different surgical techniques employed and their influence on outcomes. RECENT FINDINGS: The main debate regarding surgical technique is using bone or only soft tissue for fixation of the meniscal horns. Biomechanical and other basic science studies show improved function and less extrusion when the grafts are secured with bone. However, several clinical studies show no difference in outcomes. Long-term studies have shown improved success with less graft extrusion and may illustrate the important function of bone fixation. Many clinical studies, including those with long-term outcomes, have shown meniscal allografts can decrease patient pain and improve function. It is a technically challenging procedure with good clinical outcomes regardless of the method of graft fixation. Bone fixation provides less extrusion which is associated with improved graft function and decreased rate of joint deterioration. Further study is needed to determine if other methods to decrease extrusion are able to improve graft function and outcomes.

7.
JBJS Rev ; 11(4)2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37014938

RESUMO

¼: There is a spectrum of midtarsal injuries, ranging from mild midfoot sprains to complex Lisfranc fracture-dislocations. ¼: Use of appropriate imaging can reduce patient morbidity, by reducing the number of missed diagnoses and, conversely, avoiding overtreatment. Weight-bearing radiographs are of great value when investigating the so-called subtle Lisfranc injury. ¼: Regardless of the operative strategy, anatomical reduction and stable fixation is a prerequisite for a satisfactory outcome in the management of displaced injuries. ¼: Fixation device removal is less frequently reported after primary arthrodesis compared with open reduction and internal fixation based on 6 published meta-analyses. However, the indications for further surgery are often unclear, and the evidence of the included studies is of typically low quality. Further high-quality prospective randomized trials with robust cost-effectiveness analyses are required in this area. ¼: We have proposed an investigation and treatment algorithm based on the current literature and clinical experience of our trauma center.


Assuntos
Fraturas Ósseas , Humanos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Redução Aberta/métodos , Estudos Prospectivos , Radiografia
8.
Arthrosc Sports Med Rehabil ; 5(1): e267-e272, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36866298

RESUMO

Purpose: To evaluate the effect of graft donor age on outcomes of anterior cruciate ligament (ACL) reconstruction with nonirradiated, fresh-frozen tibialis tendon allografts. Methods: This prospective, randomized, double-blind, single surgeon, 2-year follow-up study enrolled 40 patients (28 female, 12 male who underwent ACL reconstruction with tibialis tendon allografts. Results were compared with historical outcomes for allografts from donors aged 18 to 70 years. Analysis was determined by Group A (<50 years) and Group B (>50 years). Objective and subjective International Knee Documentation Committee (IKDC) forms, KT-1000 testing, and Lysholm scores were used for the evaluation. Results: Follow-up on average of 24 months was completed in 37 patients (92.5%; Group A = 17, Group B = 20). Average patient age at surgery for Group A was 42.1 years (range 27-54) and Group B was 41.7 years (range 24-56). None of the patients required additional surgery during the initial 2-year follow-up. At 2-year follow-up, there were no significant differences in subjective outcomes. IKDC objective ratings for Group A were A-15 and B-2, and Group B were A-19 and B-1 (P = .45). Average IKDC subjective scores for Group A were 86.1 (± 16.2) and Group B were 84.1 (± 15.6) (P = .70). KT-1000 side to side differences for Group A were 0-4, 1-10, and 2-2, and Group B were 0-2, 1-10, 2-6 (P = .28). Average Lysholm scores for Group A were 91.4 (± 16.7) and Group B were 88.1 (± 12.3) (P = .49). Conclusions: Donor age was not associated with clinical outcomes after ACL reconstruction using nonirradiated, fresh-frozen tibialis tendon allografts. Level of Evidence: II, prospective prognostic trial.

9.
Ther Adv Med Oncol ; 15: 17588359231160140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970111

RESUMO

Tebentafusp is a first-in-class immunotherapy agent that comprises an engineered T-cell receptor targeting a gp100 epitope presented by human leukocyte antigen-A*02:01 cells, fused to an anti-CD3 single-chain variable fragment. Tebentafusp is both the first bispecific T-cell engager to show efficacy in the treatment of advanced solid cancer and the first anti-cancer treatment to demonstrate an overall survival benefit in patients with uveal melanoma (UM). This review article will focus on the clinical development of tebentafusp, the mechanism of action and resultant evolution of the management of advanced UM.

10.
Bone Joint J ; 105-B(2): 112-123, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36722062

RESUMO

Despite being one of the most common injuries around the elbow, the optimal treatment of olecranon fractures is far from established and stimulates debate among both general orthopaedic trauma surgeons and upper limb specialists. It is almost universally accepted that stable non-displaced fractures can be safely treated nonoperatively with minimal specialist input. Internal fixation is recommended for the vast majority of displaced fractures, with a range of techniques and implants to choose from. However, there is concern regarding the complication rates, largely related to symptomatic metalwork resulting in high rates of implant removal. As the number of elderly patients sustaining these injuries increases, we are becoming more aware of the issues associated with fixation in osteoporotic bone and the often fragile soft-tissue envelope in this group. Given this, there is evidence to support an increasing role for nonoperative management in this high-risk demographic group, even in those presenting with displaced and/or multifragmentary fracture patterns. This review summarizes the available literature to date, focusing predominantly on the management techniques and available implants for stable fractures of the olecranon. It also offers some insights into the potential avenues for future research, in the hope of addressing some of the pertinent questions that remain unanswered.Cite this article: Bone Joint J 2023;105-B(2):112-123.


Assuntos
Articulação do Cotovelo , Fraturas Ósseas , Fratura do Olécrano , Fraturas da Ulna , Idoso , Humanos , Fraturas da Ulna/cirurgia , Articulação do Cotovelo/cirurgia , Remoção de Dispositivo
11.
Ther Apher Dial ; 27(1): 170-176, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35490343

RESUMO

INTRODUCTION: After the FDA gave emergency approval for the use of therapeutic plasma exchange in treatment for SARS-Coronoavirus-2, we analyzed its efficacy in patients who had failed all other known therapies. METHODS: This was a prospective observational study of 42 patients with SARS-Coronoavirus-2 who had failed conventional therapy and were treated with therapeutic plasma exchange. Pre- and postexchange clinical and laboratory parameters were monitored. The patients were then also compared with a group of 147 patients with SARS-Coronoavirus-2 who were referred for stage 3 acute renal failure and dialysis from SARS-Coronoavirus-2. RESULTS: After therapeutic plasma exchange, there were significant improvements in some clinical parameters but mortality remained high; although better than the renal failure group (43.9% vs. 50.7%, p = 0.004). CONCLUSION: SARS-CoV-2 patients who failed all other therapies had significant mortality with therapeutic plasma exchange; however, their survival was better than SARS-CoV-2 patients with stage 3 acute renal failure.


Assuntos
Injúria Renal Aguda , COVID-19 , Humanos , SARS-CoV-2 , Troca Plasmática/efeitos adversos , COVID-19/terapia , Plasmaferese , Injúria Renal Aguda/terapia
12.
Arthroscopy ; 39(2): 384-389.e6, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36207000

RESUMO

PURPOSE: To examine the trends in physician professional fees and inpatient and outpatient facility fees in orthopaedic surgery in the United States. METHODS: Physician professional fees and inpatient and outpatient facility fees were tracked from 2008 to 2021 for the most common orthopaedic procedures in each orthopaedic subspecialty. Using common procedure codes for physician and outpatient procedures and Medicare severity diagnosis related group codes for inpatient procedures, the Medicare Physician Fee Schedules were used to obtain the national payment amounts for physician professional fees and inpatient and outpatient facility fees. Trends in fees were tracked over time after adjustment for inflation. RESULTS: From 2008 to 2021, physician professional fees decreased by an average of 20%, whereas inpatient facility fees increased by 15%, and outpatient facility fees increased by 72%. The orthopaedic subspecialty with the largest decrease in physician professional fees was oncology, with an average decrease of 23.5%, followed by general orthopaedics (23.1%), and sports medicine (22.8%). The largest increase in outpatient facility fees was seen in the subspecialties of general orthopaedics (149.8%), spine (130.1%), and trauma (123.0%). CONCLUSIONS: Over the past 13 years, physician professional fees for the most common orthopaedic procedures have declined while inpatient and outpatient facility fees have increased. Understanding these changes is important to the practice of orthopaedic surgery in the United States. LEVEL OF EVIDENCE: IV, economic.


Assuntos
Procedimentos Ortopédicos , Ortopedia , Idoso , Humanos , Estados Unidos , Medicare , Pacientes Internados , Pacientes Ambulatoriais
13.
Nat Commun ; 13(1): 2287, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484103

RESUMO

Rotational motion lies at the heart of intermolecular, molecule-surface chemistry and cold molecule science, motivating the development of methods to excite and de-excite rotations. Existing schemes involve perturbing the molecules with photons or electrons which supply or remove energy comparable to the rotational level spacing. Here, we study the possibility of de-exciting the molecular rotation of a D2 molecule, from J = 2 to the non-rotating J = 0 state, without using an energy-matched perturbation. We show that passing the beam through a 1 m long magnetic field, which splits the rotational projection states by only 10-12 eV, can change the probability that a molecule-surface collision will stop a molecule from rotating and lose rotational energy which is 9 orders larger than that of the magnetic manipulation. Calculations confirm that different rotational orientations have different de-excitation probabilities but underestimate rotational flips (∆mJ[Formula: see text]0), highlighting the importance of the results as a sensitive benchmark for further developing theoretical models of molecule-surface interactions.

14.
Bone Joint J ; 104-B(4): 452-463, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35360945

RESUMO

AIMS: Access to total knee arthroplasty (TKA) is sometimes restricted for patients with severe obesity (BMI ≥ 40 kg/m2). This study compares the cost per quality-adjusted life year (QALY) associated with TKA in patients with a BMI above and below 40 kg/m2 to examine whether this is supported. METHODS: This single-centre study compared 169 consecutive patients with severe obesity (BMI ≥ 40 kg/m2) (mean age 65.2 years (40 to 87); mean BMI 44.2 kg/m2 (40 to 66); 129/169 female) undergoing unilateral TKA to a propensity score matched (age, sex, preoperative Oxford Knee Score (OKS)) cohort with a BMI < 40 kg/m2 in a 1:1 ratio. Demographic data, comorbidities, and complications to one year were recorded. Preoperative and one-year patient-reported outcome measures (PROMs) were completed: EuroQol five-dimension three-level questionnaire (EQ-5D-3L), OKS, pain, and satisfaction. Using national life expectancy data with obesity correction and the 2020 NHS National Tariff, QALYs (discounted at 3.5%), and direct medical costs accrued over a patient's lifetime, were calculated. Probabilistic sensitivity analysis (PSA) was used to model variation in cost/QALY for each cohort across 1,000 simulations. RESULTS: All PROMs improved significantly (p < 0.05) in both groups without differences between groups. Early complications were higher in BMI ≥ 40 kg/m2: 34/169 versus 52/169 (p = 0.050). A total of 16 (9.5%) patients with a BMI ≥ 40 kg/m2 were readmitted within one year with six reoperations (3.6%) including three (1.2%) revisions for infection. Assuming reduced life expectancy in severe obesity and revision costs, TKA in patients with a BMI ≥ 40 kg/m2 costs a mean of £1,013/QALY (95% confidence interval £678 to 1,409) more over a lifetime than TKA in patients with BMI < 40 kg/m2. In PSA replicates, the maximum cost/QALY was £3,921 in patients with a BMI < 40 kg/m2 and £5,275 in patients with a BMI ≥ 40 kg/m2. CONCLUSION: Higher complication rates following TKA in severely obese patients result in a lifetime cost/QALY that is £1,013 greater than that for patients with BMI < 40 kg/m2, suggesting that TKA remains a cost-effective use of healthcare resources in severely obese patients where the surgeon considers it appropriate. Cite this article: Bone Joint J 2022;104-B(4):452-463.


Assuntos
Artroplastia do Joelho , Obesidade Mórbida , Osteoartrite do Joelho , Idoso , Artroplastia do Joelho/métodos , Feminino , Humanos , Obesidade/complicações , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Osteoartrite do Joelho/cirurgia , Anos de Vida Ajustados por Qualidade de Vida
15.
Eur J Cancer ; 166: 240-253, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35325701

RESUMO

Approximately one-third of women diagnosed with melanoma are of child-bearing age. The annual incidence of melanoma has risen steadily over the last 40 years, resulting in increasing numbers of women diagnosed with melanoma both during pregnancy, and post-partum. To date, there are no formal guidelines on the management of pregnancy associated melanoma (PAM), both early stage and metastatic. This article reviews the existing literature and provides a framework for the investigation and multidisciplinary management of PAM.


Assuntos
Melanoma , Complicações Neoplásicas na Gravidez , Neoplasias Cutâneas , Feminino , Humanos , Incidência , Melanoma/diagnóstico , Melanoma/epidemiologia , Melanoma/terapia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/terapia
16.
Elife ; 112022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35179489

RESUMO

The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed in pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal and pluripotency. How HERVH elements achieve such transcriptional specificity remains poorly understood. To uncover the sequence features underlying HERVH transcriptional activity, we performed a phyloregulatory analysis of the long terminal repeats (LTR7) of the HERVH family, which harbor its promoter, using a wealth of regulatory genomics data. We found that the family includes at least eight previously unrecognized subfamilies that have been active at different timepoints in primate evolution and display distinct expression patterns during human embryonic development. Notably, nearly all HERVH elements transcribed in ESCs belong to one of the youngest subfamilies we dubbed LTR7up. LTR7 sequence evolution was driven by a mixture of mutational processes, including point mutations, duplications, and multiple recombination events between subfamilies, that led to transcription factor binding motif modules characteristic of each subfamily. Using a reporter assay, we show that one such motif, a predicted SOX2/3 binding site unique to LTR7up, is essential for robust promoter activity in induced pluripotent stem cells. Together these findings illuminate the mechanisms by which HERVH diversified its expression pattern during evolution to colonize distinct cellular niches within the human embryo.


Assuntos
Retrovirus Endógenos , Células-Tronco Pluripotentes , Animais , Retrovirus Endógenos/genética , Genômica , Humanos , Primatas/genética , Sequências Repetidas Terminais/genética
18.
J Orthop Trauma ; 36(4): 195-200, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34483324

RESUMO

OBJECTIVES: To (1) describe the percutaneous technique used to reduce and fix a posterior malleolar fracture with anteroposterior screws in patients managed with a fibular intramedullary nail, (2) describe the selection of patients to whom this technique can be applied, and (3) report the clinical and patient reported outcome of this intervention. DESIGN: Retrospective review. SETTING: Academic orthopaedic trauma center. PATIENTS: Thirty-two consecutive patients with a mean age of 65 years (range, 39-90) over a thirteen-year period identified from a prospective database. INTERVENTION: Unstable ankle fractures managed surgically with a fibular nail and percutaneous fixation of the posterior malleolar component. MAIN OUTCOME MEASUREMENTS: The primary short-term outcome was complications related to posterior malleolar fracture fixation. The primary mid-term outcome was the Olerud-Molander Ankle Score. Secondary outcomes included the Manchester-Oxford Foot Questionnaire, EuroQol-5D, health, pain, and satisfaction. RESULTS: Thirty of the 32 (94%) posterior malleolar fractures united uneventfully. Postoperative loss of talar reduction occurred in 2 patients (6.3%), which in 1 patient (3.1%) eventually required a hindfoot nail arthrodesis. There were no soft-tissue complications related to the anteroposterior screws or the fibular nail fixation. At a mean follow-up of 3.7 years (range, 1-8), the median Olerud-Molander Ankle Score, Manchester-Oxford Foot Questionnaire, EuroQol-5D, health, pain, and satisfaction scores were 80.0, 23.4, 0.85, 80.0, 85.0, and 87.5, respectively. CONCLUSIONS: Percutaneous ankle fracture fixation with a fibular nail and posterior malleolar screws results in reliable fracture stabilization, good patient outcomes, and high treatment satisfaction. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Fraturas do Tornozelo , Adulto , Idoso , Idoso de 80 Anos ou mais , Tornozelo , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Pinos Ortopédicos , Fixação Interna de Fraturas/métodos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
BMJ Open Respir Res ; 8(1)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34493540

RESUMO

INTRODUCTION: The type of lung cancer surgery impacts on tumour manipulation during surgery and may drive dissemination of cancer cells into the vasculature, thus facilitating metastatic spread. The aim of this study was to investigate the impact of surgically induced trauma using peripheral blood from preoperative and postoperative patients with non-small cell lung cancer (NSCLC) undergoing thoracotomy or video-assisted thoracoscopic surgery (VATS) resection. METHODS: Imaging flow cytometry was used to measure circulating cancer-associated cells (CCs). Circulating cell-free DNA (ccfDNA) isolation was performed using Promega dsDNA HS Assay Kit. DNA integrity measurements were calculated by the ALU247 to ALU115 ratio and cytokine levels measured using the Luminex screening assay. RESULTS: CCs were increased in postoperative blood samples in 54 patients with NSCLC. Patients who underwent thoracotomy instead of VATS had higher numbers of EpCAM (p=0.004) and PanCK-labelled (p=0.03) CCs postoperatively. ccfDNA and DNA integrity index were also significantly increased in postoperative samples (p=0.0009 and p=0.04), with concomitant increase in interleukin 6 and interleukin 10 levels in the same cohorts (p=0.0004 and p=0.034, respectively). CONCLUSIONS: In this study we have shown the potential clinical utility of several biomarkers from liquid biopsies to guide perioperative management, as well as provide a snapshot of the type of surgical resection in terms of circulating tumour cell release. Obtaining reliable readouts from blood can provide crucial information for disease progression, as well as being of prognostic value monitoring patients' response to treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Ácidos Nucleicos Livres , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Cirurgia Torácica Vídeoassistida , Toracotomia
20.
Bone Joint J ; 103-B(7): 1284-1291, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34192926

RESUMO

AIMS: Acute distal biceps tendon repair reduces fatigue-related pain and minimizes loss of supination of the forearm and strength of flexion of the elbow. We report the short- and long-term outcome following repair using fixation with a cortical button techqniue. METHODS: Between October 2010 and July 2018, 102 patients with a mean age of 43 years (19 to 67), including 101 males, underwent distal biceps tendon repair less than six weeks after the injury, using cortical button fixation. The primary short-term outcome measure was the rate of complications. The primary long-term outcome measure was the abbreviated Disabilities of the Arm, Shoulder and Hand (QuickDASH) score. Secondary outcomes included the Oxford Elbow Score (OES), EuroQol five-dimension three-level score (EQ-5D-3L), satisfaction, and return to function. RESULTS: Eight patients (7.8%) had a major complication and 34 (33.3%) had a minor complication. Major complications included re-rupture (n = 3; 2.9%), unrecovered nerve injury (n = 4; 3.9%), and surgery for heterotopic ossification (n = 1; 1.0%). Three patients (2.9%) overall required further surgery for a complication. Minor complications included neurapraxia (n = 27; 26.5%) and superficial infection (n = 7; 6.9%). A total of 33 nerve injuries occurred in 31 patients (30.4%). At a mean follow-up of five years (1 to 9.8) outcomes were available for 86 patients (84.3%). The median QuickDASH, OES, EQ-5D-3L, and satisfaction scores were 1.2 (IQR 0 to 5.1), 48 (IQR 46 to 48), 0.80 (IQR 0.72 to 1.0), and 100/100 (IQR 90 to 100), respectively. Most patients were able to return to work (81/83, 97.6%) and sport (51/62,82.3%). Unrecovered nerve injury was associated with an inferior outcome according to the QuickDASH (p = 0.005), OES (p = 0.004), EQ-5D-3L (p = 0.010), and satisfaction (p = 0.024). Multiple linear regression analysis identified an unrecovered nerve injury to be strongly associated with an inferior outcome according to the QuickDASH score (p < 0.001), along with infection (p < 0.001), although re-rupture (p = 0.440) and further surgery (p = 0.652) were not. CONCLUSION: Acute distal biceps tendon repair using cortical button fixation was found to result in excellent patient-reported outcomes and health-related quality of life. Although rare, unrecovered nerve injury adversely affects outcome. Cite this article: Bone Joint J 2021;103-B(7):1284-1291.


Assuntos
Traumatismos do Braço/cirurgia , Âncoras de Sutura , Traumatismos dos Tendões/cirurgia , Adulto , Idoso , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Recuperação de Função Fisiológica , Estudos Retrospectivos
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