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1.
J Immunol ; 209(9): 1724-1735, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36104113

RESUMO

In this work, we have generated novel Fc-comprising NK cell engagers (NKCEs) that bridge human NKp30 on NK cells to human epidermal growth factor receptor (EGFR) on tumor cells. Camelid-derived VHH single-domain Abs specific for human NKp30 and a humanized Fab derived from the EGFR-specific therapeutic Ab cetuximab were used as binding arms. By combining camelid immunization with yeast surface display, we were able to isolate a diverse panel of NKp30-specific VHHs against different epitopes on NKp30. Intriguingly, NKCEs built with VHHs that compete for binding to NKp30 with B7-H6, the natural ligand of NKp30, were significantly more potent in eliciting tumor cell lysis of EGFR-positive tumor cells than NKCEs harboring VHHs that target different epitopes on NKp30 from B7-H6. We demonstrate that the NKCEs can be further improved with respect to killing capabilities by concomitant engagement of FcγRIIIa and that soluble B7-H6 does not impede cytolytic capacities of all scrutinized NKCEs at significantly higher B7-H6 concentrations than observed in cancer patients. Moreover, we show that physiological processes requiring interactions between membrane-bound B7-H6 and NKp30 on NK cells are unaffected by noncompeting NKCEs still eliciting tumor cell killing at low picomolar concentrations. Ultimately, the NKCEs generated in this study were significantly more potent in eliciting NK cell-mediated tumor cell lysis than cetuximab and elicited a robust release of proinflammatory cytokines, both features which might be beneficial for antitumor therapy.


Assuntos
Citocinas , Receptor 3 Desencadeador da Citotoxicidade Natural , Humanos , Antígenos B7/metabolismo , Morte Celular , Cetuximab/farmacologia , Epitopos , Receptores ErbB , Células Matadoras Naturais , Ligantes , Receptor 3 Desencadeador da Citotoxicidade Natural/metabolismo
2.
Eur J Orthop Surg Traumatol ; 34(1): 175-180, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37389708

RESUMO

INTRODUCTION: Tennis elbow management has primarily been conservative over the years with over 90% of the cases being managed conservatively. Surgical intervention may be necessary only for symptomatic recalcitrant cases of tennis elbow cases. However, there are gaps in the literature when it comes to comparison of the return to pre-operative return to their work and level of activities among patients who undergo arthroscopic management and those who receive conservative management. METHODS: A retrospective observational study was conducted to compare 23 patients receiving continued intensive conservative (CIC) management in group 1 with 24 patients undergoing arthroscopic release of the extensor carpi radialis brevis and lateral epicondyle decortication (ARD) in group 2. The study had a minimum follow-up period of 3.5 years. The researchers compared the groups in terms of return to work (RTW) at the same intensity or lower level and any changes in their previous work. Objective grip strength and patient-reported outcome measures, such as post-intervention satisfaction level (rated on a scale of 0-100) and visual analog scale (VAS) for residual elbow pain, were also compared between the two groups. RESULTS: Return to work (RTW) occurred significantly earlier in group 2 (mean 6.13 months) compared to group 1 (mean 4.64 months), and a greater number of patients in group 2 (13/24, 54.2%) were able to return to the same of work. Although not statistically significant, the ARD group exhibited comparable patient satisfaction (p = 0.62) and visual analog scale (VAS) scores for residual elbow pain (p = 0.67). Grip strength was comparable (p = 0.084, 0.121) between the affected and unaffected sides of the bilateral upper extremities and among both groups of patients. CONCLUSION: The use of ARD for RTE (recalcitrant tennis elbow) indicates a significantly earlier return to work (RTW) at the same or lower intensity level compared to the standard CIC therapy protocol. Objective grip strength was comparable to the non-affected side and among the two groups of patients receiving two different management modalities. Comparable patient-reported satisfaction and residual lateral elbow pain were also noted among both the groups. LEVEL OF EVIDENCE: Retrospective, comparative study, level III.


Assuntos
Satisfação do Paciente , Cotovelo de Tenista , Humanos , Estudos Retrospectivos , Tratamento Conservador , Cotovelo de Tenista/cirurgia , Retorno ao Trabalho , Artroscopia/métodos , Dor , Artralgia
3.
J Immunol ; 206(1): 225-236, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33268483

RESUMO

Activating NK cell receptors represent promising target structures to elicit potent antitumor immune responses. In this study, novel immunoligands were generated that bridge the activating NK cell receptor NKp30 on NK cells with epidermal growth factor receptor (EGFR) on tumor cells in a bispecific IgG-like format based on affinity-optimized versions of B7-H6 and the Fab arm derived from cetuximab. To enhance NKp30 binding, the solitary N-terminal IgV domain of B7-H6 (ΔB7-H6) was affinity matured by an evolutionary library approach combined with yeast surface display. Biochemical and functional characterization of 36 of these novel ΔB7-H6-derived NK cell engagers revealed an up to 45-fold-enhanced affinity for NKp30 and significantly improved NK cell-mediated, EGFR-dependent killing of tumor cells compared with the NK cell engager based on the wild-type ΔB7-H6 domain. In this regard, potencies (EC50 killing) of the best immunoligands were substantially improved by up to 87-fold. Moreover, release of IFN-γ and TNF-α was significantly increased. Importantly, equipment of the ΔB7-H6-based NK cell engagers with a human IgG1 Fc part competent in Fc receptor binding resulted in an almost 10-fold superior killing of EGFR-overexpressing tumor cells compared with molecules either triggering FcγRIIIa or NKp30. Additionally, INF-γ and TNF-α release was increased compared with molecules solely triggering FcγRIIIa, including the clinically approved Ab cetuximab. Thus, incorporating affinity-matured ligands for NK cell-activating receptors might represent an effective strategy for the generation of potent novel therapeutic agents with unique effector functions in cancer immunotherapy.


Assuntos
Antígenos B7/metabolismo , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/metabolismo , Neoplasias/imunologia , Anticorpos Biespecíficos/genética , Anticorpos Biespecíficos/metabolismo , Antígenos B7/genética , Linhagem Celular Tumoral , Cetuximab/genética , Citocinas/metabolismo , Citotoxicidade Imunológica , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Engenharia Genética , Humanos , Fragmentos Fab das Imunoglobulinas/genética , Mediadores da Inflamação/metabolismo , Células Matadoras Naturais/transplante , Ativação Linfocitária , Receptor 3 Desencadeador da Citotoxicidade Natural/imunologia , Neoplasias/terapia , Ligação Proteica , Transdução de Sinais
4.
Proc Natl Acad Sci U S A ; 117(11): 5588-5594, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32123085

RESUMO

The use of potassium (K) metal anodes could result in high-performance K-ion batteries that offer a sustainable and low-cost alternative to lithium (Li)-ion technology. However, formation of dendrites on such K-metal surfaces is inevitable, which prevents their utilization. Here, we report that K dendrites can be healed in situ in a K-metal battery. The healing is triggered by current-controlled, self-heating at the electrolyte/dendrite interface, which causes migration of surface atoms away from the dendrite tips, thereby smoothening the dendritic surface. We discover that this process is strikingly more efficient for K as compared to Li metal. We show that the reason for this is the far greater mobility of surface atoms in K relative to Li metal, which enables dendrite healing to take place at an order-of-magnitude lower current density. We demonstrate that the K-metal anode can be coupled with a potassium cobalt oxide cathode to achieve dendrite healing in a practical full-cell device.

5.
Eur Spine J ; 30(7): 1835-1847, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33742234

RESUMO

BACKGROUND: Hemivertebrectomy is widely used definitive correction surgery in congenital scoliosis due to hemivertebrae. It may be done either as combined anterior and posterior approach or a single-stage posterior approach only. The purpose of this meta-analysis was to compare two techniques with regards to blood loss, operative time, deformity correction and complications. METHODS: The systematic review and meta-analysis were conducted according to PRISMA guidelines among peer-reviewed journals published in English between June 2000 and June 2020. Quality appraisal of all selected articles was done and data extracted. RESULTS: After thorough literature search and excluding, 37 studies were included for review. The commonest location of the hemivertebrae was thoracolumbar spine (51.3%), thoracic (26.2%), lumbar/lumbosacral (21.6%) followed by cervical (0.7%). Pooled data showed a significant difference (p < 0.05) in mean operative time with posterior only approach (227 min, 95% CI 205-250) as compared to Combined Anterior Posterior Approach (CAPA) (316 min 95% CI 291-341). Significant difference (p < 0.05) in mean blood loss was observed in posterior only approach (522 ml, 95% CI 434-611) as compared to CAPA (888 ml, 95% CI 663-1113). No significant difference was noted in mean correction in either of the approaches and overall pooled mean correction rate was 66%, 95% CI 61-72. CONCLUSION: This review and meta-analysis of two surgical techniques of hemivertebrectomy, shows that operative time and blood loss is significantly lower in posterior only approach with no difference in correction rate as compared to CAPA. There was significant correlation between age at surgery and need for revision surgeries. LEVEL OF EVIDENCE: IV.


Assuntos
Escoliose , Fusão Vertebral , Seguimentos , Humanos , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Escoliose/cirurgia , Vértebras Torácicas/cirurgia , Resultado do Tratamento
6.
Proc Natl Acad Sci U S A ; 115(11): E2499-E2508, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29483276

RESUMO

Optical phase changes induced by transient perturbations provide a sensitive measure of material properties. We demonstrate the high sensitivity and speed of such methods, using two interferometric techniques: quantitative phase imaging (QPI) in transmission and phase-resolved optical coherence tomography (OCT) in reflection. Shot-noise-limited QPI can resolve energy deposition of about 3.4 mJ/cm2 in a single pulse, which corresponds to 0.8 °C temperature rise in a single cell. OCT can detect deposition of 24 mJ/cm2 energy between two scattering interfaces producing signals with about 30-dB signal-to-noise ratio (SNR), and 4.7 mJ/cm2 when SNR is 45 dB. Both techniques can image thermal changes within the thermal confinement time, which enables accurate single-shot mapping of absorption coefficients even in highly scattering samples, as well as electrical conductivity and many other material properties in biological samples at cellular scale. Integration of the phase changes along the beam path helps increase sensitivity, and the signal relaxation time reveals the size of hidden objects. These methods may enable multiple applications, ranging from temperature-controlled retinal laser therapy or gene expression to mapping electric current density and characterization of semiconductor devices with rapid pump-probe measurements.


Assuntos
Interferometria/métodos , Retina/química , Tomografia de Coerência Óptica/métodos , Animais , Lasers , Ratos , Ratos Long-Evans , Retina/diagnóstico por imagem , Epitélio Pigmentado da Retina/química , Epitélio Pigmentado da Retina/diagnóstico por imagem , Razão Sinal-Ruído
7.
J Intensive Care Med ; 35(8): 810-817, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30165769

RESUMO

OBJECTIVES: Early organ dysfunction in sepsis confers a high risk of in-hospital mortality, but the relative contribution of specific types of organ failure to overall mortality is unclear. The objective of this study was to assess the predictive ability of individual types of organ failure to in-hospital mortality or prolonged intensive care. METHODS: Retrospective cohort study of adult emergency department patients with sepsis from October 1, 2013, to November 10, 2015. Multivariable regression was used to assess the odds ratios of individual organ failure types for the outcomes of in-hospital death (primary) and in-hospital death or ICU stay ≥ 3 days (secondary). RESULTS: Of 2796 patients, 283 (10%) experienced in-hospital mortality, and 748 (27%) experienced in-hospital mortality or an ICU stay ≥ 3 days. The following components of Sequential Organ Failure Assessment (SOFA) score were most predictive of in-hospital mortality (descending order): coagulation (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.32-1.93), hepatic (1.58, 95% CI: 1.32-1.90), respiratory (OR: 1.33, 95% CI: 1.21-1.47), neurologic (OR: 1.20, 95% CI: 1.07-1.35), renal (OR: 1.14, 95% CI: 1.02-1.27), and cardiovascular (OR: 1.13, 95% CI: 1.01-1.25). For mortality or ICU stay ≥3 days, the most predictive SOFA components were respiratory (OR: 1.97, 95% CI: 1.79-2.16), neurologic (OR: 1.72, 95% CI: 1.54-1.92), cardiovascular (OR: 1.38, 95% CI: 1.23-1.54), coagulation (OR: 1.31, 95% CI: 1.10-1.55), and renal (OR: 1.19, 95% CI: 1.08-1.30) while hepatic SOFA (OR: 1.16, 95% CI: 0.98-1.37) did not reach statistical significance (P = .092). CONCLUSION: In this retrospective study, SOFA score components demonstrated varying predictive abilities for mortality in sepsis. Elevated coagulation or hepatic SOFA scores were most predictive of in-hospital death, while an elevated respiratory SOFA was most predictive of death or ICU stay >3 days.


Assuntos
Mortalidade Hospitalar , Insuficiência de Múltiplos Órgãos/mortalidade , Escores de Disfunção Orgânica , Sepse/mortalidade , Resultados de Cuidados Críticos , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Estudos Retrospectivos
8.
J Virol ; 89(9): 5124-33, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25717106

RESUMO

UNLABELLED: The E2F family of transcription factors, broadly divided into activator and repressor E2Fs, regulates cell cycle genes. Current models indicate that activator E2Fs are necessary for cell cycle progression and tumorigenesis and are also required to mediate transformation induced by DNA tumor viruses. E2Fs are negatively regulated by the retinoblastoma (RB) family of tumor suppressor proteins, and virus-encoded oncogenes disrupt the RB-E2F repressor complexes. This results in the release of activator E2Fs and induction of E2F-dependent genes. In agreement, expression of large tumor T antigens (TAg) encoded by polyomaviruses in mammalian cells results in increased transcriptional levels of E2F target genes. In addition, tumorigenesis induced by transgenic expression of simian virus 40 (SV40) TAg in choroid plexus or intestinal villi requires at least one activator E2F. In contrast, we show that SV40 TAg-induced transformation in mouse embryonic fibroblasts is independent of activator E2Fs. This work, coupled with recent studies showing that proliferation in stem and progenitor cells is independent of activator E2Fs, suggests the presence of parallel pathways governing cell proliferation and tumorigenesis. IMPORTANCE: The RB-E2F pathway is altered in many cancers and is also targeted by DNA tumor viruses. Viral oncoprotein action on RBs results in the release of activator E2Fs and upregulation of E2F target genes; thus, activator E2Fs are considered essential for normal and tumorigenic cell proliferation. However, we have observed that SV40 large T antigen can induce cell proliferation and transformation in the absence of activator E2Fs. Our results also suggest that TAg action on pRBs regulates both E2F-dependent and -independent pathways that govern proliferation. Thus, specific cell proliferation pathways affected by RB alterations in cancer may be a factor in tumor behavior and response to therapy.


Assuntos
Antígenos Virais de Tumores/metabolismo , Transformação Celular Viral , Fatores de Transcrição E2F/metabolismo , Fibroblastos/virologia , Vírus 40 dos Símios/fisiologia , Animais , Antígenos Virais de Tumores/genética , Proliferação de Células , Camundongos
9.
Bioorg Med Chem ; 22(22): 6490-6502, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25440730

RESUMO

Polyomavirus infections are common and relatively benign in the general human population but can become pathogenic in immunosuppressed patients. Because most treatments for polyomavirusassociated diseases nonspecifically target DNA replication, existing treatments for polyomavirus infection possess undesirable side effects. However, all polyomaviruses express Large Tumor Antigen (T Ag), which is unique to this virus family and may serve as a therapeutic target. Previous screening of pyrimidinone­peptoid hybrid compounds identified MAL2-11B and a MAL2-11B tetrazole derivative as inhibitors of viral replication and T Ag ATPase activity (IC50 of ~20-50 µM. To improve upon this scaffold and to develop a structure­activity relationship for this new class of antiviral agents, several iterative series of MAL2-11B derivatives were synthesized. The replacement of a flexible methylene chain linker with a benzyl group or, alternatively, the addition of an ortho-methyl substituent on the biphenyl side chain in MAL2-11B yielded an IC50 of 50 µM, which retained antiviral activity. After combining both structural motifs, a new lead compound was identified that inhibited T Ag ATPase activity with an IC50 of 50 µM. We suggest that the knowledge gained from the structure­activity relationship and a further refinement cycle of the MAL2-11B scaffold will provide a specific, novel therapeutic treatment option for polyomavirus infections and their associated diseases.


Assuntos
Antígenos Virais de Tumores/química , Antivirais/síntese química , Vírus 40 dos Símios/metabolismo , Bibliotecas de Moléculas Pequenas/química , Antígenos Virais de Tumores/metabolismo , Antivirais/farmacologia , Antivirais/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos , Peptoides/química , Polyomavirus/efeitos dos fármacos , Ligação Proteica , Pirimidinonas/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
10.
Arch Orthop Trauma Surg ; 134(4): 467-71, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24493466

RESUMO

Patella cubiti is a rare elbow anomaly in which either the entire olecranon or a part of it remains separate from the proximal ulna. Pain and stiffness are the usual presenting symptoms while some patients are diagnosed incidentally following a minor trauma. Our case report is of a 24-year-old male wrestler with bilateral patella cubiti which was painful on right side and asymptomatic on the left. We also mention an additional cause of pain in patella cubiti-intra-articular loose bodies. These loose bodies were removed surgically and the patient remained asymptomatic at 6-months follow-up. Presence of growth disturbance in the secondary epiphyseal centre of first lumbar vertebra supports the 'developmental theory' of origin of patella cubiti. A compilation of data available in the literature on patella cubiti has been included.


Assuntos
Articulação do Cotovelo/anormalidades , Articulação do Cotovelo/cirurgia , Olécrano/anormalidades , Olécrano/cirurgia , Adulto , Articulação do Cotovelo/fisiopatologia , Humanos , Masculino , Dor/etiologia , Dor/cirurgia , Adulto Jovem
11.
Chin J Traumatol ; 17(5): 293-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25293901

RESUMO

Controlling postoperative pain after total hip replacement is important and controversy remains regarding different regimens. By reviewing 18 studies, we attempt to find whether local infiltration analgesia after total hip replacement has any effect on postoperative pain, length of hospital stay and opioid consumption. We conclude that local infiltration analgesia is an effective method for decreasing postoperative pain.


Assuntos
Analgesia/métodos , Anestésicos Locais/uso terapêutico , Artroplastia de Quadril , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Analgésicos Opioides/uso terapêutico , Humanos , Tempo de Internação/estatística & dados numéricos , Medição da Dor
12.
Hip Pelvis ; 36(1): 12-25, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38420735

RESUMO

Protrusio acetabuli, or abnormal protrusion of the femoral head into the acetabulum, requires performance of a total hip arthroplasty (THA) for which various reconstruction techniques and outcomes have been described. The aim of this systematic review is to provide a comprehensive analysis of the current evidence, evaluate treatment efficacy, compare surgical techniques, and identify topics for future research along with improving evidence-based decision-making, improving patient outcomes in the management of this condition. A thorough systematic review of the PubMed, Embase, Cochrane Library databases, and Scopus library was conducted, and articles describing techniques of THA for treatment of protrusion acetabuli were extracted. The initial search generated 751 results. After exclusion, 18 articles were included. Of these, eight were prospective studies and 10 were retrospective. Surgery was performed on 783 hips with a mean age of 60 years; 80% of females who mostly had inflammatory arthritis were followed up for 8.86 years (range, 2-15.4 years). Good outcomes have been achieved with THA using uncemented cups with bone graft; however, no conclusion could be drawn with regard to the femoral side. It can be concluded that the concept of restoration of the anatomical hip center of rotation is paramount for good outcome and better survival of the implant is important when using uncemented cups with a bone graft. In addition, screw augmentation for fixation is not recommended unless absolutely necessary. The most common complications were aseptic loosening and heterotopic ossification. While the former required revision, conservative management was administered for the latter.

13.
Knee Surg Relat Res ; 36(1): 7, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38268011

RESUMO

PURPOSE: Patients with varus knee osteoarthritis usually compensate at the ankle and typically walk with hindfoot valgus alignment. As the neutral weight-bearing axis of the lower limbs is restored with Total Knee Arthroplasty (TKA), ankle and hindfoot biomechanics also acutely change. This study aims to investigate whether any ankle clinical-radiographical changes occur as a result of bilateral mechanical TKA in patients with bilateral Osteoarthritis knee at a minimum follow-up of 6 months. METHODS: The prospective observational study included 61 patients (122 knees) undergoing simultaneous bilateral TKA (mechanical alignment). Tibio-talar angle(TTA), tibial Anterior Surface angle (TAS), lateral distal tibial angle (LDTA), talar-tilt angle (TT), anatomical talocrural angle (aTC), ground surface and distal tibial plafond angle (GP), ground surface and an upper surface of talus angle (GT)and tibial plateau and tibial plafond angle (PP) were measured on long-film radiographs to look for changes in the ankle, whereas functional assessment was done using American Foot and Ankle Society (AOFAS), Foot and Ankle Disability Index (FADI), and Forgotten Joint (FJS-12) scores. Patients were sub-grouped based on the Hip-Knee-Ankle (HKA) axis, and the effect of the severity of knee varus on the ankles after TKA was also analyzed. The minimum follow-up was 6 months. RESULTS: A significant decrease in the tibial plateau-tibial plafond (PP), ground-tibial plafond (GP), and ground-talar dome (GT) angles was noted after TKA (p-value < 0.05). Postoperative functional parameters were comparable to the preoperative status except for FADI, which significantly improved (p-value-0.03). Sub-group analysis based on the severity of knee varus (HKA) revealed GT to be most significantly reduced (p-value-0.036), while the talar tilt (TT) increased (p-value-0.044). Functional outcomes of the ankles clinically improved with the correction of severe knee varus after TKA. At a mean follow-up of 13.2 months post-TKA, 7 out of 61 (11.4%) patients complained of post-TKA ipsilateral ankle pain. CONCLUSION: Mechanically aligned bilateral TKA in severe varus deformity of the knee significantly decreases the GT angle but increases the varus tilt of the talus with lateral talar incongruency and under-coverage. Although the acute correction of severe knee varus deformity aligns the tibia more neutrally, resulting in an overall clinically evident improvement in ankle functional outcome, the increased varus talar tilt remains a deep concern. LEVEL OF EVIDENCE: Prospective, observational, comparative study Level II.

14.
Arterioscler Thromb Vasc Biol ; 32(10): 2418-26, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22904274

RESUMO

OBJECTIVE: To evaluate direct versus indirect monocyte chemoattractant protein (MCP)-1/CCR2 signaling and to identify the cellular producers and effectors for MCP-1 during neointimal hyperplasia (NIH) development in vein grafts. METHODS AND RESULTS: Genomic analysis revealed an overrepresentation of 13 inflammatory pathways in wild-type vein grafts compared with CCR2 knockout vein grafts. Further investigation with various vein graft-host combinations of MCP-1- and CCR2-deficient mice was used to modify the genotype of cells both inside (graft-intrinsic group) and outside (graft-extrinsic group) the vein wall. CCR2 deficiency inhibited NIH only when present in cells extrinsic to the graft wall, and MCP-1 deficiency required its effectiveness in cells both intrinsic and extrinsic to the graft wall to suppress NIH. Deletion of either MCP-1 or CCR2 was equally effective in inhibiting NIH. CCR2 deficiency in the predominant neointimal cell population had no impact on NIH. Direct MCP-1 stimulation of primary neointimal smooth muscle cells had minimal influence on cell proliferation and matrix turnover, confirming an indirect mechanism of action. CONCLUSIONS: MCP-1/CCR2 axis accelerates NIH via its signaling in graft-extrinsic cells, particularly circulating inflammatory cells, with cells both intrinsic and extrinsic to the graft wall being critical MCP-1 producers. These findings underscore the importance of systemic treatment for anti-MCP-1/CCR2 therapies.


Assuntos
Quimiocina CCL2/fisiologia , Neointima/patologia , Neointima/fisiopatologia , Receptores CCR2/fisiologia , Transdução de Sinais/fisiologia , Enxerto Vascular , Animais , Artéria Carótida Primitiva/cirurgia , Proliferação de Células , Células Cultivadas , Quimiocina CCL2/deficiência , Quimiocina CCL2/farmacologia , Matriz Extracelular/fisiologia , Regulação da Expressão Gênica/fisiologia , Hiperplasia , Masculino , Camundongos , Camundongos Knockout , Modelos Animais , Receptores CCR2/deficiência , Veia Cava Inferior/cirurgia
15.
Soc Sci Humanit Open ; 8(1): 100579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37287633

RESUMO

Assessing students' online learning is a vital constituent of the effective teaching-learning process in a virtual mode. This study addressed teachers' preparedness, challenges and effective practices for students' assessment in online learning during the COVID-19 pandemic. Online assessment at times of uncertainty has become arduous for university teachers as it is not in practice in Indian higher educational institutions (HEIs). This research reports a study of the Adamas University, teachers drawn-out through semi-structured interviews of individual teachers. The researchers employed a case study research method to attain the objectives of the study using thematic analysis for the qualitative data. Thirty-one faculty members were selected as a sample of the study. The study findings indicated that the University teachers used multiple online assessment techniques, some common, some extremely unique, viz. blogs and peer tutorial videos. The preparedness or readiness varied considerably as some were instead sceptical, whereas some were amusingly non-challant. The study found that teachers faced many problems while assessing students' performance during online classes, which were not just tech-based, but also due to their distressed state of mind.

16.
J Clin Orthop Trauma ; 31: 101924, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35941870

RESUMO

Purpose: The direct anterior approach (DAA) for total hip replacement (THR) is relatively new. It has been proved superior to other techniques concerning early functional outcomes, stability, and earlier recovery. But DAA-THR has a steeper surgical learning curve and, in its original description, needs special operating room equipment. This study aims to present clinical, functional, and radiological outcomes of DAA compared to the posterior approach (PA), performed using a routine operating table and instrumentation sets. Methods: Eighty patients undergoing THR were non-randomly allocated prospectively into Group 1 DAA and Group 2 PA. Visual analog scale (VAS) for pain was recorded preoperatively and at 6, 12, 24, 48, and 72 h after the surgery and at 1st and 2nd year postoperatively. Both groups' functional outcomes were evaluated pre-and postoperatively at 1st and 2nd-year follow-up with Harris hip score (HHS) and SF-12. Perioperative parameters like blood loss, length of hospital stay, duration of surgery, postoperative complications, and radiological prosthesis positioning were also compared between the two groups. Results: All patients were comparable according to their baseline demographic characteristics. DAA was found to have significantly better early HHS at one year (p = 0.001) and VAS for hip pain (p < 0.05) at 12, 24, 48, and 72 hrs postoperative period only. Clinical outcomes were comparable at the final follow-up of 2 years. Perioperative variables were also similar except the incision length, length of stay in the hospital, and average time to weight bear without walking aids which were statistically better in DAA than PA group. There was no difference in radiological prosthesis positioning. Postoperative complication rates were also comparable in the two groups. Conclusion: Though technically demanding, DAA provides better early functional outcomes with comparable radiological outcomes and complication rates than the PA.Level of evidence: Non-randomized comparative trial, Level II.

17.
Asian Spine J ; 16(1): 9-19, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33789415

RESUMO

STUDY DESIGN: Electronic survey-based study. PURPOSE: The aim of the study was to objectively review the variability in the prevailing treatment protocols and surgical decision making in the management of patients with spinal tuberculosis (TB) among spine surgeons with expertise in spinal TB across the country. OVERVIEW OF LITERATURE: A lack of good-quality evidence, ambiguities in the national spinal TB guidelines, and the demand for early rehabilitation and a better quality of life in patients with spinal TB has led to the emergence of various gray zones in the management of spinal TB. METHODS: Seventeen fellowship-trained spinal TB experts representing different geographical regions of India completed an online survey consisting of questions pertaining to the conservative management of spinal TB (antitubercular therapy) and 30 clinical case vignettes including a wide spectrum of presentations of spinal TB with no or minimal neurological deficit. The variability in the responses for questions and case wise variability with respect to surgical decision making was assessed using the index of qualitative variation (IQV). The average tendency to operate (TTO) was calculated for various groups of respondents. RESULTS: High variability was observed in all questions regarding conservative spinal TB management (IQV > 0.8). Among the 30 case vignettes, 14 were found to have high variability with respect to surgical decision making (IQV > 0.8). With respect to levels of fixation, all but two cases had poor or slight agreement. Younger age and practice in a government or tertiary care teaching hospital were factors associated with a higher TTO. CONCLUSIONS: Significant variability was detected in treatment practices for the management of spinal TB among experts. Most of the case vignettes were found to have significant heterogeneity with respect to surgical decision making, which reflects a significant lack of consensus and lacunae in literature.

18.
Strategies Trauma Limb Reconstr ; 17(2): 74-80, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990184

RESUMO

Background: Various modalities of treatment have been used for the management of metacarpal and phalangeal fractures which include K-wire fixation, mini plates, lag screws fixation, intramedullary screw fixation and external fixator application. The aim of this study was to analyse complications and patient-related functional outcomes after antegrade or retrograde crossed intramedullary K-wire fixation of metacarpal and proximal phalangeal fractures. Methods: Thirty-one patients (36-fractures, 16-metacarpals, 20-proximal phalanx) meeting the study criteria were included in this prospective study. Fixation of the fractures was done by use of crossed intramedullary K-wire using the principles of 3-point fixation. Results: The mean preoperative angulation of the fractures noted in this study was 35.8° which was significantly reduced at final follow-up. Union was noted at a mean period of 4.2 ± 6.8 weeks. The mean range of motion at the metacarpophalangeal and proximal interphalangeal joint was 96.4% and 86.3%, respectively as compared to the opposite hand. Stiffness (n = 3, 14.2%) and persistent pain (n = 2, 9.5%) at the joints were the most common complications noted in this study. Conclusion: Crossed percutaneous intramedullary fixation of small bone fractures of the hand is a versatile method with advantages such as cost-effectiveness and lesser operative time when compared to other modalities of fixation. Earlier range of motion (ROM) exercises can be started due to preservation of gliding planes, no surgical wound along with good fracture stability and minimal hardware impingement. How to cite this article: Ahmad S, Gupta T, Ansari S, et al. Intramedullary Crossed K-wire Fixation for the Hand Fractures is a Useful Treatment Modality: A Prospective Observational Study. Strategies Trauma Limb Reconstr 2022;17(2):74-80.

19.
Nat Commun ; 13(1): 282, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022390

RESUMO

Metal-organic frameworks (MOFs) are commended as photocatalysts for H2 evolution and CO2 reduction as they combine light-harvesting and catalytic functions with excellent reactant adsorption capabilities. For dynamic processes in liquid phase, the accessibility of active sites becomes a critical parameter as reactant diffusion is limited by the inherently small micropores. Our strategy is to introduce additional mesopores by selectively removing one ligand in mixed-ligand MOFs via thermolysis. Here we report photoactive MOFs of the MIL-125-Ti family with two distinct mesopore architectures resembling either large cavities or branching fractures. The ligand removal is highly selective and follows a 2-step process tunable by temperature and time. The introduction of mesopores and the associated formation of new active sites have improved the HER rates of the MOFs by up to 500%. We envision that this strategy will allow the purposeful engineering of hierarchical MOFs and advance their applicability in environmental and energy technologies.

20.
Hip Pelvis ; 33(1): 3-10, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33748020

RESUMO

There is no clear evidence on indications and outcomes of hip arthroscopy in sequelae of Legg-Calve-Perthes disease (LCPD). The aim of the current study was to evaluate current literature on the role and outcome of hip arthroscopy in LCPD. A literature search using four databases was conducted in April 2020, focusing on the role of hip arthroscopy in sequelae of LCPD. A systematic search was carried out in confirmation with the Cochrane Collaboration, Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of nine studies were included in the systematic review. The total number of hip arthroscopies performed for LCPD was 109. The mean age of included patients was 34.8±7.88 years (7-58 years). Recalcitrant hip pain was the main indication for surgery, followed by pain and stiffness. The most common finding in arthroscopy was labral tears, followed by osteochondral lesions of femoral head or acetabulum and intra-articular loose bodies. Consequently, debridement of labrum tears chondroplasty for cartilage defects and osteoplasty for impingement from deformed femoral head (hinged abduction) were commonly performed. A significant improvement in hip function was seen in all studies. Pooled data of Harris hip score showed significant improvement after surgery was conducted. Hip arthroscopy may be beneficial in patients having symptoms of impingement secondary to changes in labrum, femoral head or acetabulum. Limited evidence shows improved function and range of motion after surgery. This treatment has been found to be safe in terms of complication rates and improvement may persist for years.

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