Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids.

Highly effective vaccines elicit specific, robust, and durable adaptive immune responses. To advance informed vaccine design, it is critical that we understand the cellular dynamics underlying responses to different antigen formats. Here, we sought to understand how antigen-specific B and T cells were activated and participated in adaptive immune responses within the mucosal site. Using a human tonsil organoid model, we tracked the differentiation and kinetics of the adaptive immune response to influenza vaccine and virus modalities. Each antigen format elicited distinct B and T cell responses, including differences in their magnitude, diversity, phenotype, function, and breadth. These differences culminated in substantial changes in the corresponding antibody response. A major source of antigen format-related variability was the ability to recruit naive vs. memory B and T cells to the response. These findings have important implications for vaccine design and the generation of protective immune responses in the upper respiratory tract.

Enhancement of factor VIIa haemostatic efficacy by formulation with PEGylated liposomes.

Recombinant activated factor VII (rFVIIa) is an effective treatment of the haemophilia patient with inhibitors and acquired haemophilia. However, on account of its relatively short half-life (HL), achieving therapeutic efficacy with FVIIa requires repeated injections. The development of a long-acting FVIIa product would therefore be beneficial. The formulation of factor VIII with PEGylated liposomes (PEGLip) was previously shown to extend the bleeding-free period in haemophilia patients. We report here an enhancement of haemostatic efficacy by similarly formulating FVIIa with PEGLip. Surface plasmon resonance analysis indicated that FVIIa binds non-covalently but with high affinity and specificity to PEGLip. A one-stage clotting assay demonstrated that formulation of FVIIa with PEGLip does not affect FVIIa activity and stability. A pharmacokinetic study in rats demonstrated that PEGLip formulation of FVIIa extends circulation time and results in higher FVIIa levels several hours after injection. Thromboelastography experiments indicated that PEGLip-FVIIa induces faster clot formation and higher clot stability than standard formulated FVIIa. These results suggest that formulation of FVIIa with PEGLip may lead to a safe and effective long-acting FVIIa that improves the care of haemophilic patients with inhibitors and acquired haemophilia.

Further aspects of design for distal extension removable partial dentures based on the Kennedy classification.

A supplement to the Kennedy classification of partially edentulous arches for restoration with removable partial dentures has been suggested. Factors affecting denture design relating to the position of the abutment teeth, the symmetry of the edentulous distal extensions, the arch form and the cross-sectional shape of the residual ridges have been discussed and classified. An understanding of the movement of the denture bases in relation to the influence of these factors makes for a rational approach to removable partial denture design and the treatment of complications observed clinically in removable partial denture wearers.

Use of roots to establish favorable removable partial denture design: case reports.

Judicious retention of roots can alter the position of the anterior fulcrum line and so simplify removable partial denture design. Complicated tooth-tissue-supported designs are thus transformed into much simpler tooth-supported removable partial overdentures.

The cantilever fixed partial denture--a literature review.

The cantilever fixed partial denture (FPD) is a restoration with one or more abutments at one end and unsupported at the other end. Forces transmitted through the cantilevered pontics can cause tilting and rotational movements of the abutments. In a cross-arch unilateral cantilever FPD, the distal cantilevered unit is subjected to comparatively less force than the contralateral posterior abutment. The unilateral lack of terminal abutments causes lateral bending forces activate peripheral inhibitory feedback reactions from the periodontal and/or temporomandibular mechanoreceptors. The greatest strain in distal cantilevered FPDs is recorded mesial to the most distal retainer because most fractures occur in this location. To improve the prognosis of the FPD cantilever, the number of abutments should be increased and the number of pontics decreased. The abutment teeth need long roots and acceptable alveolar support. Prepared abutments require adequate length and parallel axial walls. An equilibrated and harmonious occlusion is necessary, as well as exemplary oral hygiene. A cantilevered FPD with adequate periodontal support can replace any tooth in the dental arch, but is especially useful as an alternative to a removable partial denture. The cantilevered FPD requires at least two abutment teeth. The only documented exception permitting a single abutment is the replacement of a maxillary lateral incisor with the canine as an abutment. An alternative to the cantilevered FPD is the osseointegrated implant. As osseointegrated implants become more popular, the need for the tooth-supported cantilevered FPD may decline, but it will remain an alternative treatment modality.

Factors affecting displacement of free-end saddle removable partial dentures.

Tissueward movement of the free-end saddle of a removable partial denture during function takes place around the most distal fulcrum created by the most mesial rests. Displacement because of sticky foods takes place around the fulcrum created by the most distal rests. These and other factors affecting displacement of the free-end saddle removable partial dentures are discussed, and designs intended to increase retention are presented. The forces applied to the most anterior and posterior axes of rotation can be calculated mathematically to reveal the hazards of a too-short lever arm in combination with a strong retentive clasp system.

RLS--the lingually retained clasp assembly for distal extension removable partial dentures.

The design of clasp for a distal extension removable partial denture that helps preserve both the abutment teeth and the tissues of the edentulous ridge is described. The clasp assembly takes advantage of surveyed lingual undercuts to provide support, retention, and stability. It consists of a mesio-occlusal rest, a distolingual L-bar direct retainer that is located on the abutment tooth adjacent to the residual ridge, and a distobuccal stabilizer (RLS).

Rigidity of major connectors when subjected to bending and torsion forces.

Rigidity tests were performed on maxillary major connectors of different designs and mandibular major connectors of the lingual bar-type with different cross-sectional shapes and thicknesses. Each major connector was clamped on one side while the other side was subjected to bending, torsion, and bending under torsion forces. Deformation was measured with a micrometer microscope. The most rigid maxillary major connector was the design incorporating the anterior-posterior palatal bar. The most flexible was the U-shaped palatal bar. The full pear-shaped lingual bar (4 x 4 mm) was the most rigid of the major connectors. Among the more conventional lingual bars, the semielliptical bar (3.75 X 1.75 mm) was the most rigid, and the narrow semielliptical bar (4 x 1.5 mm) was the most flexible.

Photoelastic analysis of stress transfer by endodontically treated teeth to the supporting structure using different restorative techniques.

A photoelastic model was used to examine the influence of different types of restorations placed following endodontic therapy, emphasizing the way in which forces applied to the occlusal surface were dispersed to the supporting structures of the teeth. Stresses were photographed in the polarized light field. Findings indicate that distribution and patterns of stresses vary depending on the direction of the loads and the nature of the involved restorative procedures.

Severe infraclusion ankylosis: report of three cases.

Tooth ankylosis may occur at any time during eruption and may show varying degrees of infraclusion. Cases of fully erupted teeth subsequently becoming totally embedded in bone are rare. The three reports described here show cases of severe infraclusion ankylosis; the etiology and related problems are discussed. Associated periodontal, prosthetic and orthodontic problems can be avoided with early diagnosis and treatment.

An analysis of rotational movement of asymmetrical distal-extension removable partial dentures.

An axis of rotation is created through the most distally placed occlusal rests when a distal-extension removable partial denture is loaded. If the residual ridges are of unequal lengths, this axis of rotation may not be perpendicular to the residual ridges. The resultant movement of asymmetric denture bases and their effect on the tissues are discussed. Movement of I-bar retainers located on the mesiobuccal aspect of asymmetrical abutment teeth may torque the abutment teeth as the denture base moves tissueward. Use of L-shaped direct retainers on the distobuccal surveyed undercut will create a more favorable class II lever effect on the abutment tooth.

A rapid dowel core construction technique.

The use of composite resins for dowel cementation and core construction is well established. A short, easy, time-saving method is proposed for simultaneous dowel cementation and core fabrication using a composite core construction material.

A modified direct retainer design for distal-extension removable partial dentures.

The rationale for designing a direct retainer for a distal-extension removable partial denture is described. The advantages of an L-bar clasp arm over the I-bar clasp arm are discussed. The retentive surface of an abutment tooth is divided into three zones according to the clasp tip movement and the importance of placing the retentive tip in the zone of vertical movement is emphasized.