Results of monovision correction in bilateral pseudophakes

We performed a retrospective study of the postoperative use of glasses in 100 patients with bilateral posterior chamber implants. Patients' vision had been corrected with one emmetropic eye and one myopic eye for simultaneous distance and near vision without glasses. The number of patients wearing bifocals preoperatively declined by half with this technique. Postoperatively, 11% of patients wore glasses out of habit, even though their visual acuities were equivalent to those of the 14% who subjectively needed no correction after surgery. The results of the study and the advantages of this monovision method of optical correction in bilateral pseudophakes are discussed.     

A comprehensive three-dimensional dynamic model of the human head and trunk for estimating lumbar and cervical joint torques and forces from upper body kinematics

Linked-segment representations of human body dynamics have been used extensively in biomechanics, ergonomics, and rehabilitation research to systemize thinking, make predictions, and suggest novel experiments. In the scope of upper body biomechanics, these models play an even more essential role as the human spine dynamics are difficult to study in vivo. No study exists to date, however, that specifically disseminates the technical details of a comprehensive three-dimensional model of the upper body for the purpose of estimating spinal joint torques and forces for a wide range of scenarios. Consequently, researchers are still bound to develop and implement their own models. Therefore, the objective of this study was to design a dynamic model of the upper body that can comprehensively estimate spinal joint torques and forces from upper body kinematics. The proposed three-dimensional model focuses on the actions of the lumbar and cervical vertebrae and consists of five lumbar segments (L1 to L5), the thorax, six cervical segments (C2 to C7), and the head. Additionally, the model: (1) is flexible regarding the kinematic nature of the spinal joints (free, constrained, or fixed); (2) incorporates all geometric and mass-inertia parameters from a single, high-resolution source; and (3) can be feasibly implemented via different inverse dynamics formulations. To demonstrate its practicality, the model was finally employed to estimate the lumbar and cervical joint torques during perturbed sitting using experimental motion data. Considering the growing importance of mathematical predictions, the developed model should become an important resource for researchers in different fields.     

Codon optimization of human factor VIII cDNAs leads to high-level expression

Gene therapy for hemophilia A would be facilitated by development of smaller expression cassettes encoding factor VIII (FVIII), which demonstrate improved biosynthesis and/or enhanced biologic properties. B domain deleted (BDD) FVIII retains full procoagulant function and is expressed at higher levels than wild-type FVIII. However, a partial BDD FVIII, leaving an N-terminal 226 amino acid stretch (N6), increases in vitro secretion of FVIII tenfold compared with BDD-FVIII. In this study, we tested various BDD constructs in the context of either wild-type or codon-optimized cDNA sequences expressed under control of the strong, ubiquitous Spleen Focus Forming Virus promoter within a self-inactivating HIV-based lentiviral vector. Transduced 293T cells in vitro demonstrated detectable FVIII activity. Hemophilic mice treated with lentiviral vectors showed expression of FVIII activity and phenotypic correction sustained over 250 days. Importantly, codon-optimized constructs achieved an unprecedented 29- to 44-fold increase in expression, yielding more than 200% normal human FVIII levels. Addition of B domain sequences to BDD-FVIII did not significantly increase in vivo expression. These significant findings demonstrate that shorter FVIII constructs that can be more easily accommodated in viral vectors can result in increased therapeutic efficacy and may deliver effective gene therapy for hemophilia A.     

Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes

TNFRSF13B encodes transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a B cell- specific tumor necrosis factor (TNF) receptor superfamily member. Both biallelic and monoallelic TNFRSF13B mutations were identified in patients with common variable immunodeficiency disorders. The genetic complexity and variable clinical presentation of TACI deficiency prompted us to evaluate the genetic, immunologic, and clinical condition in 50 individuals with TNFRSF13B alterations, following screening of 564 unrelated patients with hypogammaglobulinemia. We identified 13 new sequence variants. The most frequent TNFRSF13B variants (C104R and A181E; n=39; 6.9%) were also present in a heterozygous state in 2% of 675 controls. All patients with biallelic mutations had hypogammaglobulinemia and nearly all showed impaired binding to a proliferation-inducing ligand (APRIL). However, the majority (n=41; 82%) of the pa-tients carried monoallelic changes in TNFRSF13B. Presence of a heterozygous mutation was associated with antibody deficiency (P< .001, relative risk 3.6). Heterozygosity for the most common mutation, C104R, was associated with disease (P< .001, relative risk 4.2). Furthermore, heterozygosity for C104R was associated with low numbers of IgD(-)CD27(+) B cells (P= .019), benign lymphoproliferation (P< .001), and autoimmune complications (P= .001). These associations indicate that C104R heterozygosity increases the risk for common variable immunodeficiency disorders and influences clinical presentation.     

Motivational interviewing to support antiretroviral therapy adherence: the role of quality counseling

OBJECTIVE: Although research linking motivational interviewing (MI) to behavior change exists, few studies report on MI's quality or explore how it may influence effectiveness. We studied MI quality and adherence to antiretroviral therapy (ART) in the context of a randomized, controlled trial. METHODS: We used a structured instrument to code MI sessions and then correlated ART adherence (measured by electronic bottle cap monitor and pill count data at study exit) with specific counseling behaviors and the proportion of interactions that achieved quality benchmarks. RESULTS: The sample (n = 47) was predominantly male (79%), minority (90%), had a mean age of 40, and averaged 79% adherence at exit. On three of five benchmarks, most MI sessions achieved the targeted quality level: 100% achieved them for MI-consistent statements; 85% for complex reflections; 63% for reflections to questions ratio; 44% for global therapist rating; 19% for using open-ended questions. ART adherence was positively associated with the ratio of reflections to questions (r = .39, p = .02), affirming statements (r = .38, p = .02), and negatively associated with closed-ended questions (r = -.33, p = .04). DISCUSSION: Good quality MI can be conducted within the structure of a controlled trial but was generally not associated with ART adherence. CONCLUSION: Documenting treatment fidelity is critical to judging the efficacy of MI-based interventions. PRACTICE IMPLICATIONS: Regular feedback and close monitoring are needed to maintain MI quality.