Amino acids 484 and 494 of SARS-CoV-2 spike are hotspots of immune evasion affecting antibody but not ACE2 binding

Understanding SARS-CoV-2 evolution and host immunity is critical to control COVID-19 pandemics. At the core is an arms-race between SARS-CoV-2 antibody and angiotensin-converting enzyme 2 (ACE2) recognition, a function of the viral protein spike. Mutations in spike impacting antibody and/or ACE2 binding are appearing worldwide, with the effect of mutation synergy still incompletely understood. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations, and confirmed that E484K evades antibody neutralization elicited by infection or vaccination, a capacity augmented when complemented by K417N and N501Y mutations. In silico analysis provided an explanation for E484K immune evasion. E484 frequently engages in interactions with antibodies but not with ACE2. Importantly, we identified a novel amino acid of concern, S494, which shares a similar pattern. Using the already circulating mutation S494P, we found that it reduces antibody neutralization of convalescent and post-immunization sera, particularly when combined with E484K and N501Y. Our analysis of synergic mutations provides a landscape for hotspots for immune evasion and for targets for therapies, vaccines and diagnostics. One-Sentence SummaryAmino acids in SARS-CoV-2 spike protein implicated in immune evasion are biased for binding to neutralizing antibodies but dispensable for binding the host receptor angiotensin-converting enzyme

Conservative Esthetic Approach of Anterior Teeth Using Minimal Intervention and Preservation of all Sound Tooth Tissue: a Case Report / Abordagem Estética Conservadora dos Dentes Anteriores Utilizando Intervenção Mínima e Preservação de Todo o Tecido Dentário Sadio: Relato de Caso

This clinical case report describes a conservative approach to a smile harmony rehabilitation performing a gingivoplasty, dental bleaching and resin-based composites to finalize the case. This clinical article describes the case report of a patient in need of an esthetic and corrective solution for the anterior teeth, which presented a disharmonic smile, in its shape and color, besides the gingival smile. As a result, gingivoplasty, dental bleaching and restoration with composite resin were done. Gingivoplasty with bone preservation was possible because there was a large volume of soft tissue, and a distance ≥ 2 mm from the bone crest to the junction cementum enamel was confirmed. Bleaching was performed with the use of associated techniques: office (Whiteness HP 35%) and supervised at-home (Whiteness Perfect 10%) bleaching were performed, and then the "buccolingual technique" using a nanocomposite resin IPS was used from a diagnostic wax-up to perform the restorative procedure for the anterior teeth. The use of minimally invasive techniques is an effective alternative for the anterior teeth rehabilitation. As in this case, the gingivoplasty, dental bleaching with associated techniques, and restorations with nanocomposites allowed satisfactory esthetic results, even more so in relation to dental preservation, mainly in young patients. (AU)

Este relato de caso clínico descreve uma abordagem conservadora de uma reabilitação para harmonia do sorriso que foi realizado com gengivoplastia, clareamento dentário e resinas compostas para finalizar o caso. Este artigo clínico descreve o relato de caso de uma paciente com necessidade de solução estética e corretiva para os dentes anteriores, que apresentava um sorriso desarmônico, em sua forma e cor além do sorriso gengival. Como resultado, gengivoplastia, clareamento dental e restauração com resina composta foram realizados. A gengivoplastia com preservação óssea foi possível por apresentar grande volume de tecidos moles e uma distância ≥ 2 mm, desde a crista óssea até a junção do cemento esmalte. Clareamento com o uso de técnicas associadas: Clareamento de consultório (Whiteness HP 35%) e caseiro supervisionado (Whiteness Perfect 10%) foram realizados, e depois, a "técnica da barreira palatina" utilizando a resina IPS Empress direta foi realizada a partir de um enceramento diagnóstico para iniciar o procedimento restaurador dos dentes anteriores. O uso de técnicas minimamente invasivas é uma alternativa eficaz para reabilitação de dentes anteriores. Como no caso, a gengivoplastia, o clareamento dental com técnicas associadas e restaurações com nanocompósitos têm permitido resultados estéticos satisfatórios, ainda mais em relação à preservação dentária, principalmente em pacientes jovens. (AU)

Effect of intracanal medications on the interfacial properties of reparative cements.

OBJECTIVES: The purpose of the present study was to evaluate the effect of calcium hydroxide with 2% chlorhexidine gel (HCX) or distilled water (HCA) compared to triple antibiotic paste (TAP) on push-out bond strength and the cement/dentin interface in canals sealed with White MTA Angelus (WMTA) or Biodentine (BD). MATERIALS AND METHODS: A total of 70 extracted human lower premolars were endodontically prepared and randomly divided into 4 groups according to the intracanal medication, as follows: group 1, HCX; group 2, TAP; group 3, HCA; and group 4, control (without intracanal medication). After 7 days, the medications were removed and the cervical third of the specimens was sectioned into five 1-mm sections. The sections were then sealed with WMTA or BD as a reparative material. After 7 days in 100% humidity, a push-out bond strength test was performed. Elemental analysis was performed at the interface, using energy-dispersive spectroscopy. The data were statistically analyzed using analysis of variance and the Tukey test (p < 0.05). RESULTS: BD presented a higher bond strength than WMTA (p < 0.05). BD or WMTA in canals treated with calcium hydroxide intracanal medications had the highest bond strength values, with a statistically significant difference compared to TAP in the WMTA group (p < 0.05). There were small amounts of phosphorus in samples exposed to triple antibiotic paste, regardless of the coronal sealing. CONCLUSIONS: The use of intracanal medications did not affect the bond strength of WMTA and BD, except when TAP was used with WMTA.

Effect of intracanal medications on the interfacial properties of reparative cements

OBJECTIVES: The purpose of the present study was to evaluate the effect of calcium hydroxide with 2% chlorhexidine gel (HCX) or distilled water (HCA) compared to triple antibiotic paste (TAP) on push-out bond strength and the cement/dentin interface in canals sealed with White MTA Angelus (WMTA) or Biodentine (BD). MATERIALS AND METHODS: A total of 70 extracted human lower premolars were endodontically prepared and randomly divided into 4 groups according to the intracanal medication, as follows: group 1, HCX; group 2, TAP; group 3, HCA; and group 4, control (without intracanal medication). After 7 days, the medications were removed and the cervical third of the specimens was sectioned into five 1-mm sections. The sections were then sealed with WMTA or BD as a reparative material. After 7 days in 100% humidity, a push-out bond strength test was performed. Elemental analysis was performed at the interface, using energy-dispersive spectroscopy. The data were statistically analyzed using analysis of variance and the Tukey test (p < 0.05). RESULTS: BD presented a higher bond strength than WMTA (p < 0.05). BD or WMTA in canals treated with calcium hydroxide intracanal medications had the highest bond strength values, with a statistically significant difference compared to TAP in the WMTA group (p < 0.05). There were small amounts of phosphorus in samples exposed to triple antibiotic paste, regardless of the coronal sealing. CONCLUSIONS: The use of intracanal medications did not affect the bond strength of WMTA and BD, except when TAP was used with WMTA.

O inapanhável objeto do savoir-faire na análise / The elusory object of know-how in analysis

Além das regras técnicas, o savoir-faire (saber-fazer) provém de uma posição ética. O tato, assim como a disponibilidade, o constitui. Ele encontra sua expressão na regra da atenção igualmente em suspenso. Esta visa a impedir a compreensão precipitada e favorece a surpresa no discurso, sinais de uma passagem de inconsciente. Ela também indica que o savoir-faire se encontra ligado ao tempo e ao seu manejo, bem como à existência da lalíngua (lalangue). No entanto, o savoir-faire não deve se situar somente do lado do analista, mas também do analisante. A este cabe aprender como lidar com seu fantasma e seu sintoma. Além disso, o savoir-faire se refere sempre a uma subjetividade, seja ela do analista ou do analisante, na medida em que o inconsciente é um savoir-faire com a lalíngua?(AU)

Over and above technical rules, know-how derives from an ethical position. Tact and receptiveness are its constituent parts. It finds expression in the rule of equally suspended attention which guards against a hasty understanding of what is said, preferring surprises as signs of the unconscious. The rule indicates also that know-how is linked to the notion of time and its handling as well as to the existence of lalangue.?Know-how however is not only in the realm of the analyst. The analysand too must find how to do with his fantasies and symptom. Finally, is know-how always to be attributed to a subjectivity, be it that of the analyst’s or the analysand’s, insofar as the unconscious is know-how with lalangue?(AU)