RESUMO
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.
Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/virologia , Domínios e Motivos de Interação entre Proteínas/genética , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/isolamento & purificação , Enzima de Conversão de Angiotensina 2/ultraestrutura , Animais , Linhagem Celular Tumoral , Cristalografia por Raios X , Células HEK293 , Humanos , Simulação de Dinâmica Molecular , Mutação , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestrutura , SARS-CoV-2/genética , Células Sf9 , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Spodoptera , Ressonância de Plasmônio de Superfície , Ligação Viral , Internalização do VírusRESUMO
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.
Assuntos
Discotomia/reabilitação , Vértebras Lombares/cirurgia , Manipulações Musculoesqueléticas/estatística & dados numéricos , Adulto , Feminino , Seguimentos , Humanos , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Dor/cirurgia , Medição da Dor , Projetos Piloto , Período Pós-Operatório , Resultado do TratamentoRESUMO
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.
Assuntos
Discotomia , Deslocamento do Disco Intervertebral/reabilitação , Deslocamento do Disco Intervertebral/cirurgia , Manipulação da Coluna , Cuidados Pós-Operatórios , Adulto , Idoso , Feminino , Humanos , Terapia a Laser , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Escala Visual AnalógicaRESUMO
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.
