The effect of maternal antibodies on the cellular immune response after infant vaccination: A review

During the last few decades, maternal immunization as a strategy to protect young infants from infectious diseases has been increasingly recommended, yet some issues have emerged. Studies have shown that for several vaccines, such as live attenuated, toxoid and conjugated vaccines, high maternal antibody titers inhibit the infant’s humoral immune response after infant vaccination. However, it is not clear whether this decreased antibody titer has any clinical impact on the infant’s protection, as the cellular immune responses are often equally important in providing disease protection and may therefore compensate for diminished antibody levels. Reports describing the effect of maternal antibodies on the cellular immune response after infant vaccination are scarce, probably because such studies are expensive, labor intensive and utilize poorly standardized laboratory techniques. Therefore, this review aims to shed light on what is currently known about the cellular immune responses after infant vaccination in the presence of high (maternal) antibody titers both in animal and human studies. Overall, the findings suggest that maternally derived antibodies do not interfere with the cellular immune responses after infant vaccination. However, more research in humans is clearly needed, as most data originate from animal studies.     

OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis

PurposeNephrolithiasis (NL) affects 1 in 11 individuals worldwide, leading to significant patient morbidity. NL is associated with nephrocalcinosis (NC), a risk factor for chronic kidney disease. Causative genetic variants are detected in 11% to 28% of NL and/or NC, suggesting that additional NL/NC-associated genetic loci await discovery. Therefore, we employed genomic approaches to discover novel genetic forms of NL/NC.MethodsExome sequencing and directed sequencing of the OXGR1 locus were performed in a worldwide NL/NC cohort. Putatively deleterious, rare OXGR1 variants were functionally characterized.ResultsExome sequencing revealed a heterozygous OXGR1 missense variant (c.371T>G, p.L124R) cosegregating with calcium oxalate NL and/or NC disease in an autosomal dominant inheritance pattern within a multigenerational family with 5 affected individuals. OXGR1 encodes 2-oxoglutarate (α-ketoglutarate [AKG]) receptor 1 in the distal nephron. In response to its ligand AKG, OXGR1 stimulates the chloride-bicarbonate exchanger, pendrin, which also regulates transepithelial calcium transport in cortical connecting tubules. Strong amino acid conservation in orthologs and paralogs, severe in silico prediction scores, and extreme rarity in exome population databases suggested that the variant was deleterious. Interrogation of the OXGR1 locus in 1107 additional NL/NC families identified 5 additional deleterious dominant variants in 5 families with calcium oxalate NL/NC. Rare, potentially deleterious OXGR1 variants were enriched in patients with NL/NC compared with Exome Aggregation Consortium controls (χ² = 7.117, P = .0076). Wild-type OXGR1-expressing Xenopus oocytes exhibited AKG-responsive Ca²⁺ uptake. Of 5 NL/NC-associated missense variants, 5 revealed impaired AKG-dependent Ca²⁺ uptake, demonstrating loss of function.ConclusionRare, dominant loss-of-function OXGR1 variants are associated with recurrent calcium oxalate NL/NC disease.     

Hospital to Home Transition for Patients With Stroke Under Bundled Payments

Bundled payments are a promising alternative payment model for reducing costs and improving the coordination of postacute stroke care, yet there is limited evidence supporting the effectiveness of bundled payments for stroke. This may be due to the lack of effective strategies to address the complex needs of stroke survivors. In this article, we describe COMprehensive Post-Acute Stroke Services (COMPASS), a comprehensive transitional care intervention focused on discharge from the acute care setting to home. COMPASS may serve as a potential care redesign strategy under bundled payments for stroke, such as the Centers for Medicare & Medicaid Innovation Bundled Payment for Care Improvement Initiative. The COMPASS care model is aligned with the incentive structures and essential components of bundled payments in terms of care coordination, patient assessment, patient and family involvement, and continuity of care. Ongoing evaluation will inform the design of incorporating COMPASS-like transitional care interventions into a stroke bundle.     

Comparative antibacterial activity of topical antiseptic eardrops against methicillin-resistant Staphylococcus aureus and quinolone-resistant Pseudomonas aeruginosa

ObjectiveAural irrigation using antiseptic solutions can be an effective medical treatment of chronic suppurative otitis media (CSOM) owing to the increasing prevalence of antibiotic-resistant CSOM infections. In the present study, we compared the antimicrobial activities of 100% Burow's solution, 50% Burow's solution, 2% acetic acid, vinegar with water (1:1), and 4% boric acid solution against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), quinolone-resistant Pseudomonas aeruginosa (QRPA), and quinolone-susceptible P. aeruginosa (QSPA) in vitro.MethodsWe examined the antimicrobial activities of five antiseptic solutions against MRSA, MSSA, QRPA, and QSPA. The antimicrobial activities of the solutions were calculated as a percentage of the surviving microorganisms by dividing the viable count in each antiseptic solution with that in control. The time (D₁₀ value) required for each of the five solutions to inactivate 90% of the microorganism population was also investigated.ResultsBurow's solution exhibited the highest antimicrobial activity and the lowest D₁₀ value against MRSA, MSSA, QRPA, and QSPA, followed by 2% acetic acid, vinegar with water (1:1), and 4% boric acid solution.ConclusionOur results indicate that Burow's solution has the most potent activity against bacteria including antibiotic-resistant strains. Twofold dilution of the solution is recommended to avoid ototoxicity.     

Differential expression and functions of microRNAs in liver transplantation and potential use as non-invasive biomarkers

MicroRNAs (miRNAs) are important regulators in many biologic processes and have been implicated in the control of genes relevant to acute rejection and liver functions. Here we review the miRNAs specifically expressed in allografts during acute rejection and discuss potential roles for these miRNAs in liver dysfunction. We focus on miRNAs dysregulated both in the liver and in peripheral blood mononuclear cells and include a discussion of the potential for these miRNAs as non-invasive biomarkers to reflect liver status posttransplant.     

Extracting general practice data for timely vaccine coverage estimates: The England experience

In England, primary care providers use standardised coding systems to record health events such as vaccination as well as patient characteristics. This information can be automatically extracted to estimate coverage for vaccine programmes delivered through primary care, in the general population as well as in specific geographical, ethnic, age or clinical groups. This system provides timely vaccine coverage estimates as well as the flexibility to extract tailored data in order to directly inform a continuously evolving national vaccine programme. It is however limited by the quality and completeness of clinical coding in primary care. A centralised, individual-level register would however improve data quality, completeness and reliability and remains the gold standard.     

Drug delivery system design and development for boron neutron capture therapy on cancer treatment

We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,l-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content.