Underappreciated layers of antibody-mediated immune synapse architecture and dynamics.

The biologic activities of antibody drugs are dictated by structure-function relationships-emerging from the kind, composition, and degree of interactions with a target antigen and with soluble and cellular antibody receptors of the innate immune system. These activities are canonically understood to be both modular: antigen recognition is driven by the heterodimeric antigen-binding fragment, and innate immune recruitment by the homodimeric constant/crystallizable fragment. The model that treats these domains with a high degree of independence has served the field well but is not without limitations.

Identification of Risk Factors Associated with Early Discontinuation of Physical Therapy Following Shoulder Surgery.

Background: Postoperative physical therapy (POPT) is a critical aspect of patient recovery following orthopedic shoulder surgery. Despite the importance of POPT, some patients do not complete their course of physical therapy, which can affect postoperative recovery and outcomes. This study aimed to identify risk factors that influence patient adherence and attendance of POPT.

Multiplexed no-wash cellular imaging using BenzoTag, an evolved self-labeling protein.

Self-labeling proteins are powerful tools for exploring biology as they enable the precise cellular localization of a synthetic molecule, often a fluorescent dye. HaloTag7 is the most popular self-labeling protein due to its broad utility, its bio-orthogonality, and the simplicity of its chloroalkane ligand. However, reaction rates of HaloTag7 with different chloroalkane-containing substrates are highly variable and rates are only very fast for rhodamine-based dyes.

Exploring neuroglial signaling: diversity of molecules implicated in microglia-to-astrocyte neuroimmune communication.

Effective communication between different cell types is essential for brain health, and dysregulation of this process leads to neuropathologies. Brain glial cells, including microglia and astrocytes, orchestrate immune defense and neuroimmune responses under pathological conditions during which interglial communication is indispensable. Our appreciation of the complexity of these processes is rapidly increasing due to recent advances in molecular biology techniques, which have identified numerous phenotypic states of both microglia and astrocytes.

BenzoHTag, a fluorogenic self-labeling protein developed using molecular evolution.

Self-labeling proteins are powerful tools in chemical biology as they enable the precise cellular localization of a synthetic molecule, often a fluorescent dye, with the genetic specificity of a protein fusion. HaloTag7 is the most popular self-labeling protein due to its fast labeling kinetics and the simplicity of its chloroalkane ligand. Reaction rates of HaloTag7 with different chloroalkane-containing substrates is highly variable and rates are only very fast for rhodamine-based dyes.

Sex- and species-associated differences in complement-mediated immunity in humans and rhesus macaques.

The complement system can be viewed as a "moderator" of innate immunity, "instructor" of humoral immunity, and "regulator" of adaptive immunity. While sex is known to affect humoral and cellular immune systems, its impact on complement in humans and rhesus macaques, a commonly used non-human primate model system, has not been well studied. To address this knowledge gap, we analyzed serum samples from 90 humans and 72 rhesus macaques for the abundance and activity of the complement system components.

The Association Between Black vs. White Race and 30-Day Hospitalization Among People Diagnosed with COVID-19 Within an Integrated Care Setting: a Cohort Study.

Background: Black Americans are more likely to experience hospitalization from COVID-19 compared with White Americans. Whether this excess risk differs by age, sex, obesity, or diabetes, key risk factors for COVID hospitalization, among an integrated population with uniform healthcare access, are less clear.

Methods: We identified all adult members (≥ 18 years) of Kaiser Permanente Georgia (KPGA) diagnosed with COVID-19 between January 1, 2020, and September 30, 2021 (N = 24,564).

Silk fibroin, gelatin, and human placenta extracellular matrix-based composite hydrogels for 3D bioprinting and soft tissue engineering.

Background: There is a great clinical need and it remains a challenge to develop artificial soft tissue constructs that can mimic the biomechanical properties and bioactivity of natural tissue. This is partly due to the lack of suitable biomaterials. Hydrogels made from human placenta offer high bioactivity and represent a potential solution to create animal-free 3D bioprinting systems that are both sustainable and acceptable, as placenta is widely considered medical waste.

Sex and species associated differences in Complement-mediated immunity in Humans and Rhesus macaques.

The complement system can be viewed as a 'moderator' of innate immunity, 'instructor' of humoral immunity, and 'regulator' of adaptive immunity. While sex and aging are known to affect humoral and cellular immune systems, their impact on the complement pathway in humans and rhesus macaques, a commonly used non-human primate model system, have not been well-studied. To address this knowledge gap, we analyzed serum samples from 90 humans and 75 rhesus macaques for the abundance and activity of the complement system components.

Features of functional and dysfunctional CD8+ T cells to guide HIV vaccine development.

Purpose Of Review: CD8+ T cell responses are a key component of the host immune response to human immunodeficiency virus (HIV) but vary significantly across individuals with distinct clinical outcomes. These differences help inform the qualitative features of HIV-specific CD8+ T cells that we should aim to induce by vaccination.

Recent Findings: We review previous and more recent findings on the features of dysfunctional and functional CD8+ T cell responses that develop in individuals with uncontrolled and controlled HIV infection, with particular emphasis on proliferation, cytotoxic effector function, epitope specificity, and responses in lymph nodes.

Complement contributes to antibody-mediated protection against repeated SHIV challenge.

The first clinical efficacy trials of a broadly neutralizing antibody (bNAb) resulted in less benefit than expected and suggested that improvements are needed to prevent HIV infection. While considerable effort has focused on optimizing neutralization breadth and potency, it remains unclear whether augmenting the effector functions elicited by broadly neutralizing antibodies (bNAbs) may also improve their clinical potential. Among these effector functions, complement-mediated activities, which can culminate in the lysis of virions or infected cells, have been the least well studied.

Evidence for the Role of a Second Fc-Binding Receptor in Placental IgG Transfer in Nonhuman Primates.

Transplacental transfer of maternal antibodies provides the fetus and newborn with passive protection against infectious diseases. While the role of the highly conserved neonatal Fc receptor (FcRn) in transfer of IgG in mammals is undisputed, recent reports have suggested that a second receptor may contribute to transport in humans. We report poor transfer efficiency of plant-expressed recombinant HIV-specific antibodies, including engineered variants with high FcRn affinity, following subcutaneous infusion into rhesus macaques close to parturition.

Infraspinatus Muscle Fiber Moment Arms During Abduction: A Biomechanical Comparison of Values for Intact Rotator Cuff, Supraspinatus Tear, Superior Capsular Reconstruction, and Reverse Total Shoulder Arthroplasty.

Background: Lines of action of the superior, middle, and inferior infraspinatus muscle fibers work together to produce moment arms that change throughout abduction in an intact shoulder, after a supraspinatus tear, and after superior capsular reconstruction (SCR) and reverse total shoulder arthroplasty (rTSA).

Purpose: To use moment arm values to indicate the efficacy of SCR and rTSA to restore infraspinatus function during shoulder abduction.

Study Design: Descriptive laboratory study.

Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis.

Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential.

Revisiting an IgG Fc Loss-of-Function Experiment: the Role of Complement in HIV Broadly Neutralizing Antibody b12 Activity.

The role of the complement system in HIV-1 immunity and pathogenesis is multifaceted, and an improved understanding of complement activities mediated by HIV-1-specific antibodies has the potential to inform and advance clinical development efforts. A seminal nonhuman primate challenge experiment suggested that complement was dispensable for the protective effect of the early broadly neutralizing antibody (bnAb) b12, but recent experiments have raised questions about the breadth of circumstances under which this conclusion may hold. Here, we reassess the original observation using Fc variants of IgG1 b12 that enhance complement activity and report that complement fixation on recombinant antigen, virions, and cells and complement-dependent viral and cellular lysis vary among bnAbs.

Evaluation of rotator cuff abduction moment arms for superior capsular reconstruction and reverse total shoulder arthroplasty.

Purpose: The rotator cuff (RC) muscles contribute to dynamic stability and rotational actions of the glenohumeral joint. Moment arm can be used to demonstrate the potential work a muscle contributes to a musculoskeletal joint rotation. This study aimed to understand the moment arm contributions of the RC muscles and explore changes following a complete supraspinatus tear treated with either superior capsular reconstruction (SCR) or reverse total shoulder arthroplasty (rTSA).

Effects of implant rotational malposition on contact surface area after implantation of the augmented glenoid baseplate in the setting of glenoid bone loss.

Aim Of The Study: Augmented glenoid baseplates are utilized in reverse total shoulder arthroplasty in the setting of glenoid bone loss. These implants permit lateralization of the joint line and correction of bony version abnormalities. To allow bone preservation in the setting of abnormal bony version or deficiency, the backside of the augmented glenoid baseplate is not perpendicular to the axis of the central post/screw.

Polyfunctional Tier 2-Neutralizing Antibodies Cloned following HIV-1 Env Macaque Immunization Mirror Native Antibodies in a Human Donor.

Vaccine efforts to combat HIV are challenged by the global diversity of viral strains and shielding of neutralization epitopes on the viral envelope glycoprotein trimer. Even so, the isolation of broadly neutralizing Abs from infected individuals suggests the potential for eliciting protective Abs through vaccination. This study reports a panel of 58 mAbs cloned from a rhesus macaque () immunized with envelope glycoprotein immunogens curated from an HIV-1 clade C-infected volunteer.

Biomechanics in an Incomplete Versus Complete Supraspinatus Tear: A Cadaveric Study.

Background: Degenerative and traumatic changes to the rotator cuff can result in massive and irreparable rotator cuff tears (RCTs).

Purpose/hypothesis: The study objective was to conduct a biomechanical comparison between a small, incomplete RCT and a large, complete RCT. We hypothesized that the incomplete supraspinatus (SS) tear would lead to an incremental loss of abduction force and preserve vertical position of the humeral head, while a complete SS tear would cause superior humeral migration, decrease functional deltoid abduction force, and increase passive range of motion (ROM).

1-D imaging of rotation-vibration non-equilibrium from pure rotational ultrafast coherent anti-Stokes Raman scattering.

We present one-dimensional (1-D) imaging of rotation-vibration non-equilibrium measured by two-beam pure rotational hybrid femtosecond/picosecond coherent anti-Stokes Raman scattering (fs/ps CARS). Simultaneous measurements of the spatial distribution of molecular rotation-vibration non-equilibrium are critical for understanding molecular energy transfer in low temperature plasmas and hypersonic flows. However, non-equilibrium CARS thermometry until now was limited to point measurements.

Biomechanical effects of superior capsular reconstruction in a rotator cuff-deficient shoulder: a cadaveric study.

Background: Superior capsular reconstruction (SCR) has been gaining popularity as a treatment for irreparable rotator cuff tears (RCTs), especially in younger patients. This biomechanical study aimed to investigate how SCR affects functional abduction force, humeral head migration, and passive range of motion following an irreparable RCT. We hypothesized that SCR will restore these parameters to nearly intact shoulder levels.

The biomechanics of the supraspinatus-deficient shoulder treated with superior capsular reconstruction vs. reverse total shoulder arthroplasty-experimental study.

Aim Of The Study: Our objective was to compare biomechanical effects of superior capsular reconstruction (SCR) and reverse total shoulder arthroplasty (rTSA) on shoulder motion, in the setting of an irreparable supraspinatus (SS) tear. We hypothesized that rTSA would produce greater improvement in abduction force and shift the humerus inferiorly, while SCR would produce greater range of motion (ROM) and prevent superior migration of the humerus during abduction.

Methods: Six cadaveric shoulders were evaluated using a custom biomechanical apparatus.

Electric field vector measurements via nanosecond electric-field-induced second-harmonic generation.

Electric-field-induced second-harmonic generation, or E-FISH, has received renewed interest as a nonintrusive tool for probing electric fields in gas discharges and plasmas using ultrashort laser pulses. An important contribution of this work lies in establishing that the E-FISH method works effectively in the nanosecond regime, yielding field sensitivities of about a kV/cm at atmospheric pressure from a 16 ns pulse. This is expected to broaden its applicability within the plasma community, given the wider access to conventional nanosecond laser sources.

Antibody-mediated complement activation in pathology and protection.

Antibody-dependent complement activity is associated not only with autoimmune morbidity, but also with antitumor efficacy. In infectious disease, both recombinant monoclonal antibodies and polyclonal antibodies generated in natural adaptive responses can mediate complement activity to protective, therapeutic or disease-enhancing effect. Recent advances have contributed to the structural resolution of molecular complexes involved in antibody-mediated complement activation, defining the avid nature of participating interactions and pointing to how antibody isotype, subclass, hinge flexibility, glycosylation state, amino acid sequence and the contextual nature of the cognate antigen/epitope are all factors that can determine complement activity through impact on antibody multimerization and subsequent recruitment of complement component 1q.

In Hospital Outcomes of Total Hip Arthroplasty in the Medicaid Population.

Total hip arthroplasty (THA) is one of the most common orthopaedic procedures. This study's purpose was to evaluate national trends, patient demographics and hospital outcomes for Medicaid patients who underwent a primary THA. The National Hospital Discharge Survey (NHDS) database was queried for patients undergoing THA from 2001-2010.