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1.
Nat Commun ; 12(1): 6103, 2021 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-34671049

RESUMEN

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/virología , Dominios y Motivos de Interacción de Proteínas/genética , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Secuencia de Aminoácidos , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/aislamiento & purificación , Enzima Convertidora de Angiotensina 2/ultraestructura , Animales , Línea Celular Tumoral , Cristalografía por Rayos X , Células HEK293 , Humanos , Simulación de Dinámica Molecular , Mutación , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestructura , SARS-CoV-2/genética , Células Sf9 , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/aislamiento & purificación , Glicoproteína de la Espiga del Coronavirus/ultraestructura , Spodoptera , Resonancia por Plasmón de Superficie , Acoplamiento Viral , Internalización del Virus
3.
J Back Musculoskelet Rehabil ; 30(5): 999-1004, 2017 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-28505954

RESUMEN

BACKGROUND: Studies have shown late post-operative physical disability and residual pain in patients following lumbar disc surgery despite growing evidence of its beneficial effects. Therefore, rehabilitation is required to minimise the late post-operative complications. OBJECTIVE: To assess the feasibility of manipulative rehabilitation to improve late post-operative outcomes. METHODS: Twenty-one patients aged 25-65 years undergoing lumbar microdiscectomy were randomly assigned to the rehabilitation group (n= 14) or active control group (n= 7) by simple randomisation. Eight rehabilitation sessions were initiated 2-3 weeks after surgery. Thirty-minute sessions were conducted twice weekly for four weeks. Post-operative physical disability and pain were assessed at baseline and at the two-year follow-up. RESULTS: Post-operative physical disability improved more in patients who had undergone rehabilitation than in those who had received control care (63% vs. -23%, P< 0.05). Post-operative residual low back and leg pain were alleviated in the treatment group (26% and 57%, respectively), but intensified in the control group (-5% and -8%, respectively). CONCLUSIONS: This study demonstrated the potential of manipulative rehabilitation and importance of post-operative management after lumbar disc surgery. Definitive trials with larger sample sizes are required to confirm the feasibility and potential therapeutic effectiveness of this approach.


Asunto(s)
Discectomía/rehabilitación , Vértebras Lumbares/cirugía , Manipulaciones Musculoesqueléticas/estadística & datos numéricos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Región Lumbosacra , Masculino , Persona de Mediana Edad , Dolor/cirugía , Dimensión del Dolor , Proyectos Piloto , Periodo Posoperatorio , Resultado del Tratamiento
4.
J Back Musculoskelet Rehabil ; 29(1): 23-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-25792303

RESUMEN

BACKGROUND: Lumbar open laser microdiscectomy has been shown to be an effective intervention and safe approach for lumbar disc prolapse. However early post-operative physical disability affecting daily activities have been sporadically reported. OBJECTIVE: To evaluate the feasibility of using early individualised manipulative rehabilitation to improve early post-operative functional disability following lumbar discectomy. METHODS: Randomised controlled pilot trial. Setting at a major metropolitan spine surgery hospital. Twenty-one patients aged 25-69 years who underwent lumbar microdiscectomy were randomised to either the manipulative rehabilitation treatment group or the active control group. Rehabilitation was initiated 2-3 weeks after surgery, twice a week for 4 weeks. Each session was for 30 minutes. Primary outcomes were the Roland-Morris disability questionnaire and the visual analogue pain scale. Outcome measures were assessed at baseline and post-intervention. RESULTS: Early post-operative physical disability was improved with a 55% reduction by early individualised manipulative rehabilitation, compared to that of control care with a 5% increase. Early post-operative residual leg pain decreased with rehabilitation (55%) and control care (9%). CONCLUSION: This pilot study supports the feasibility of a future definitive randomised control trial and indicates this type of rehabilitation may be an important option for post-operative management after spinal surgery.


Asunto(s)
Discectomía , Desplazamiento del Disco Intervertebral/rehabilitación , Desplazamiento del Disco Intervertebral/cirugía , Manipulación Espinal , Cuidados Posoperatorios , Adulto , Anciano , Femenino , Humanos , Terapia por Láser , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Proyectos Piloto , Escala Visual Analógica
5.
J Korean Neurosurg Soc ; 49(6): 381-3, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21887401

RESUMEN

Sporadic osseous hemangioblastomas in the vertebra are extremely rare and they can be misdiagnosed as a vertebral hemangioma or metastasis in imaging studies. We report an intraosseous hemangioblastoma that arose from the 11th thoracic vertebra and was diagnosed initially as a metastasis in a patient with renal cell carcinoma. Diagnosis, surgical treatment and adjuvant radiosurgery of such case in reference to the literature are discussed.

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