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BACKGROUND: Vaccine development against Chlamydia, a prevalent sexually transmitted infection (STI), is imperative due to its global public health impact. However, significant challenges arise in the production of effective subunit vaccines based on recombinant protein antigens, particularly with membrane proteins like the Major Outer Membrane Protein (MOMP). METHODS: Cell-free protein synthesis (CFPS) technology is an attractive approach to address these challenges as a method of high-throughput membrane protein and protein complex production coupled with nanolipoprotein particles (NLPs). NLPs provide a supporting scaffold while allowing easy adjuvant addition during formulation. Over the last decade, we have been working toward the production and characterization of MOMP-NLP complexes for vaccine testing. RESULTS: The work presented here highlights the expression and biophysical analyses, including transmission electron microscopy (TEM) and dynamic light scattering (DLS), which confirm the formation and functionality of MOMP-NLP complexes for use in animal studies. Moreover, immunization studies in preclinical models compare the past and present protective efficacy of MOMP-NLP formulations, particularly when co-adjuvanted with CpG and FSL1. CONCLUSION: Ex vivo assessments further highlight the immunomodulatory effects of MOMP-NLP vaccinations, emphasizing their potential to elicit robust immune responses. However, further research is warranted to optimize vaccine formulations further, validate efficacy against Chlamydia trachomatis, and better understand the underlying mechanisms of immune response.

Background: Volar radiocarpal instability is often seen after loss of fixation of volar lunate facet fragments. The pathogenesis of post-traumatic volar radiocarpal instability is poorly understood. The purpose of this study was to determine if injury to the dorsal wrist extrinsic carpal ligaments contributes to volar radiocarpal instability. Methods: Six matched pairs of cadaveric upper extremities were tested using a dynamic hand testing system. In group 1, the intact wrist, the wrist with a volar lunate facet fracture, and the fractured wrist after 500 cycles of grip were tested. In group 2, in addition to the intact and fractured wrist, the fractured wrist with the dorsal extrinsic carpal ligaments cut and the fractured wrist with the dorsal extrinsic carpal ligaments cut after 500 cycles of grip were also tested. Volar-dorsal displacement of the lunate was measured from 45° wrist flexion to 45° wrist extension in 22.5° increments with the wrist flexors/extensors loaded for each condition. Results: Volar lunate translation did not significantly increase after the volar lunate facet fracture alone, and was not evident to a significant extent until the dorsal wrist extrinsic carpal ligaments were cut. Further instability of the lunate occurred after grip cycling only with the dorsal extrinsic capsular ligaments cut. Conclusions: Injury to the dorsal wrist extrinsic carpal ligaments exacerbates volar radiocarpal instability. Unrecognized dorsal sided injury may be a contributing factor to why stable fixation of volar lunate facet fragments remains problematic after volar plating of intra-articular distal radius fractures with displaced volar lunate facet fragments.

The DAMIC-M (DArk Matter In CCDs at Modane) experiment employs thick, fully depleted silicon charged-coupled devices (CCDs) to search for dark matter particles with a target exposure of 1 kg-year. A novel skipper readout implemented in the CCDs provides single electron resolution through multiple non-destructive measurements of the individual pixel charge, pushing the detection threshold to the eV-scale. DAMIC-M will advance by several orders of magnitude the exploration of the dark matter particle hypothesis, in particular of candidates pertaining to the so-called "hidden sector." A prototype, the Low Background Chamber (LBC), with 20g of low background Skipper CCDs, has been recently installed at Laboratoire Souterrain de Modane and is currently taking data. We will report the status of the DAMIC-M experiment and first results obtained with LBC commissioning data.

The genetic code is the foundation for all life. With few exceptions, the translation of nucleic acid messages into proteins follows conserved rules, which are defined by codons that specify each of the 20 proteinogenic amino acids. For decades, leading research groups have developed a catalogue of innovative approaches to extend nature's amino acid repertoire to include one or more noncanonical building blocks in a single protein. In this review, we summarize advances in the history of in vitro and in vivo genetic code expansion, and highlight recent innovations that increase the scope of biochemically accessible monomers and codons. We further summarize state-of-the-art knowledge in engineered cellular translation, as well as alterations to regulatory mechanisms that improve overall genetic code expansion. Finally, we distill existing limitations of these technologies into must-have improvements for the next generation of technologies, and speculate on future strategies that may be capable of overcoming current gaps in knowledge. [ABSTRACT FROM AUTHOR]

Abstract Background Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. Methods TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. Results Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. Conclusion TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

An operationally simple, reliable, and cheap Sonogashira reaction suitable for an undergraduate laboratory class that can be completed within a day-long (8 h) laboratory session has been developed. Cross-coupling is carried out between 2-methyl-3-butyn-2-ol and various aryl iodides using catalytic amounts of bis(triphenylphosphine)palladium(II) dichloride, with copper(I) iodide as a cocatalyst, in triethylamine at room temperature, so a range of products can be prepared within a single group and results compared. The coupling itself is usually complete within 1.5 h and is easily monitored by TLC, leaving up to 6 h for purification and characterization. Purification is by "mini flash column chromatography" through a plug of silica encased in the barrel of a plastic syringe, so the procedure is amenable to large class sizes.

Background: Women with lower extremity amputations (LEAs) tend to have poorer prosthesis‐related outcomes than men, although the literature is sparse. To our knowledge, there are no prior studies examining prosthesis‐related outcomes of women veterans with LEAs. Objective: To examine gender differences (overall and by type of amputation) among veterans who underwent LEAs between 2005 and 2018, received care at the Veterans Health Administration (VHA) prior to undergoing amputation, and were prescribed a prosthesis. It was hypothesized that compared to men, women would report lower satisfaction with prosthetic services, poorer prosthesis fit, lower prosthesis satisfaction, less prosthesis use, and worse self‐reported mobility. Furthermore, it was hypothesized that gender differences in outcomes would be more pronounced among individuals with transfemoral than among those with transtibial amputations. Design: Cross‐sectional survey. Linear regressions were used to assess overall gender differences in outcomes and gender differences based on type of amputation in a national sample of veterans. Setting: VHA medical centers. Participants: The sample consisted of 449 veterans who self‐identified their gender (women = 165, men = 284) with transtibial (n = 236), transfemoral (n = 135), and bilateral LEAs (n = 68) including all amputation etiologies. Interventions: Not applicable. Main Outcome Measures: The Orthotics and Prosthetics User's Survey, Trinity Amputation and Prosthesis Experiences Scale, and Prosthetic Limb Users Survey of Mobility‐Short Form were used to assess satisfaction with prosthetic services, prosthesis fit, prosthesis satisfaction, prosthesis use, and self‐reported mobility. Results: Women had poorer self‐reported mobility than men (d = −0.26, 95% confidence interval −0.49 to −0.02, p <.05); this difference was small. There were no statistically significant gender differences in satisfaction with prosthetic services, prosthesis fit, prosthesis satisfaction, daily hours of prosthesis use, or by amputation type. Conclusions: Contrary to the hypothesis, prosthesis‐related outcomes were similar between men and women with LEAs. Minimal differences may in part be due to receiving care from the VHA's integrated Amputation System of Care. [ABSTRACT FROM AUTHOR]

Background: Spin is defined as the use of specific reporting strategies to highlight the beneficial effect of a treatment despite nonsignificant results. The presence of spin in peer-reviewed literature can negatively impact clinical and research practices. The purpose of this study was to identify the quantity and types of spin present in primary studies and systematic reviews using suture tape augmentation for ankle instability as a model. Methods: This study was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each abstract was assessed for the presence of the 15 most common types of spin. Extracted data included study title, authors, publication year, journal, level of evidence, study design, funding, reported adherence to PRISMA guidelines, and PROSPERO registration. Full texts of systematic reviews were used in the assessment of study quality per A Measurement Tool to Assess Systematic Reviews Version 2 (AMSTAR 2). Results: Nineteen studies were included in the final sample. At least 1 type of spin was identified in each study except one (18 of 19, 94.7%). The most common type of spin observed was type 3 ("selective reporting or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention") (6 of 19, 31.6%), The second most reported category of spin was type 4 ("the conclusion claims safety based on non-statistically significant results with a wide confidence interval") (4 of 19, 21.1%). Among systematic reviews, we identified type 5 ("the conclusion claims the beneficial effect of the experimental treatment despite a high risk of bias in primary studies") in 4 out of 6 (66.7%) of the articles that were included. No significant associations were found between study characteristics and type of spin. Conclusion: In this exploration of the introduction of a new technology, we identified spin to be highly present in the abstracts of primary studies and systematic reviews concerning suture tape augmentation for ankle instability. Steps should be taken by scientific journals to ensure that spin is minimized in the abstract to accurately reflect the quality of the intervention. [ABSTRACT FROM AUTHOR]

Glycoanalysis is important in the manufacture and quality control of protein therapeutics. An emerging method for glycoanalysis is the use of lectin arrays. Critical to the performance of these arrays is the immobilization of lectin molecules. Polydopamine has recently been shown to adsorb to a wide variety of surfaces. In this study, polydopamine (pDA) was used to modify gold, indium, and iridium surfaces and promote the adhesion of the [alpha]-mannose-specific lectin concanavalin A (Con A). The activity of the surface-bound lectin was demonstrated with the [alpha]-mannose-presenting glycoprotein ribonuclease B (RNase B). Surface plasmon resonance spectroscopy (SPRS) was used to demonstrate the selective affinity of RNase B for Con A. Surface-MALDI-TOF MS experiments revealed that the affinity of polydopamine-immobilized Con A for the glycoforms of RNase B is significantly affected by slight variations in oligosaccharide structure and composition. Specifically, surface-bound Con A binds certain Man7, Man8, and Man9 RNase B glycoforms more strongly than Man5 and Man6 glycoforms.