Generation of recombinant hyperimmune globulins from diverse B-cell repertoires.

Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply and batch-to-batch variation. Here we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates of diverse mixtures of thousands of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors or from immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in under 3 months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease.

The Role of the Nurse Practitioner and Asymptomatic Urinary Treatments.

Asymptomatic urinary tract infections (aUTIs) are common among older adults in long-term care facilities (LTCFs) and studies have shown that they are inappropriately treated with antibiotics. We retrospectively characterized treatment strategies among 89 cases of aUTIs before and after a long-term facility hired a full-time nurse practitioner (NP). We found that residents with aUTIs were prescribed significantly more supportive treatment strategies after hiring an NP. However, there was no significant drop in the rate of inappropriate antibiotic treatments for aUTIs after hiring an NP.

Nicaragua: an example of commitments and strengths despite problems of poverty.

Nicaragua is located in the middle of the Central American isthmus between the countries of Honduras and Costa Rica. It is the largest Central American country and is equivalent in size to the state of Georgia. Nicaragua is cited by Pan American Health Organization as one of the poorest third-world countries. One factor that continues to contribute to Nicaragua's chronic poverty state is the demographics of the country. Nearly half of all Nicaraguans are under 15 years of age, and more than a quarter are between the ages of 15 and 29 years. Only a quarter of the population is over 30 years of age. Beyond the hardship and poverty, there is a country rich in beauty. Nicaragua has a beautiful countryside with lush green mountains, black sand beaches of the Pacific Ocean, and the natural wonder of active volcanoes. It is easy to become engulfed by the tranquility of these surroundings and to steer away from the harsh conditions of the country. It is, however, a temporary escape from reality, for it was the hardships and unfavorable circumstances of this country that are never forgotten and which persist until today. This article focuses on a variety of interventions used to assist Nicaragua with their health care and state of well-being.

Evaluation of an ion-exchange membrane for the purification of plasmid DNA.

Separation and purification of large quantities of plasmid DNA (pDNA) is a particularly difficult manufacturing issue because of the relatively low capacity, flow rate and purity observed using traditional bead-based chromatography. The objective of the present study was to evaluate the performance of anion-exchange membranes for the purification of pDNA from Escherichia coli lysate solution. The fate of host-cell protein and endotoxin relative to pDNA was measured and used to calculate recoveries, mass balances, dynamic capacities and purification factors as a function of the flow rate and loading volume of the lysate solution. Breakthrough curves were not sigmoidal and symmetric in shape. They rose sharply at first, and then slowly towards, but never reaching, saturation. Conversely, elution curves were independent of flow rate. pDNA bound tightly to the membranes, whereas protein and endotoxin did not. Dynamic binding capacity for pDNA was 20-25 times greater, and the flow rate was 55-550 times greater, than values observed for beads. However, some pDNA bound irreversibly to the membrane surface and was not removed completely during elution. The intrinsic rate of pDNA adsorption to the membrane was found to be rate-limiting, whereas effects of liquid-phase mass transfer and flow non-idealities were negligible. These results were interpreted using models of adsorption that included steric effects using the 'car-parking-problem' model, and surface residence time effects using the spreading model. This work demonstrated the advantages of ion-exchange membranes compared with beads for the purification of large biomolecules such as pDNA.