Partial NK cell tolerance induced by radioresistant host cells in rats transplanted with MHC-mismatched bone marrow

We have studied the effect of radioresistant host cells in inducing tolerance and adaptation of the MHC recognition repertoire of donor-derived NK cells in stem cell allotransplanted (allo-SCT) rats. Sub-lethally irradiated PVG.1AV1 rats (RT1(av1)) were transplanted with bone marrow from fully MHC-mismatched allotype-marked PVG.7B (RT1(c)) rats; MHC-identical PVG (RT1(c)) controls were transplanted in parallel. In the PVG.7B → PVG.1AV1 allogeneic chimeras, NK cells were donor derived and showed partial tolerance toward host cells. Allogeneic chimeras failed to efficiently reject PVG.1AV1 cells by an NK-mediated mechanism in vivo (allogeneic lymphocyte cytotoxicity), and IL-2-cultured NK cells derived from these chimeras showed diminished cytolytic activity against PVG.1AV1 cells in vitro. There were corresponding changes in the phenotype and function of the highly alloreactive Ly49i2(+) NK cells, which are specifically inhibited by a donor MHC class I ligand, RT1-A1(c). The ligand-negative host MHC haplotype apparently induced expression of a second uncharacterized inhibitory MHC receptor responsible for the partial tolerance toward host-derived cells, along with a modest increase in Ly49i2 receptor levels. The host MHC haplotype did not induce a general hyporesponsiveness in Ly49i2(+) NK cells, which showed normal activation responses in a panel of MHC congenic strains. The data suggest that the MHC constitution of radiation-resistant host cells can have permanent, albeit not fully tolerogenic, effects on the development of a functional NK repertoire following allo-SCT.     

Neonatal lesions of the ventral hippocampus in rats lead to prefrontal cognitive deficits at two maturational stages

This experiment assessed the effect of neonatal ventral hippocampus lesions in rats, a heuristic approach to model schizophrenia, on continuous delayed alternation and conditional discrimination learning performance before and after complete cerebral maturation. Delays (0, 5, 15, and 30 s) were introduced in the tasks to help dissociate between a hippocampal and a prefrontal cortex dysfunction. At postnatal day (PND) 6 or 7, rats received bilateral microinjections of ibotenic acid or phosphate-buffered saline in the ventral hippocampus. From PND 26 to PND 35, rats were tested on the alternation task in a T-maze; from PND 47 to PND 85, the same rats were tested in the discrimination task where a stimulus and a response location had to be paired. Deficits in ventral hippocampus-lesioned rats were observed in both tasks whether a delay was introduced before a response or not. Impaired performance regardless of delay length, combined with high rates of perseverative errors, suggested a post-lesional prefrontal cortex dysfunction which persisted from the juvenile stage into adulthood. Premature cognitive impairments could not be predicted on the basis of the neurodevelopmental animal model of schizophrenia. Nevertheless, they appear consistent with accounts of premorbidly compromised memory, both immediate and delayed, in subgroups of schizophrenia patients.     

Artificial-infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease

Vaccination with recombinant outer surface protein A (OspA) from Borrelia burgdorferi provides excellent antibody-mediated protection against challenge with the pathogen in animal models and in humans. However, the bactericidal antibodies are ineffective in the reservoir host, since OspA is expressed by spirochetes only in the vector, but rarely, if at all, in mammals. Using an artificially generated immune serum (anti-10(8) spirochetes) with high protective potential for prophylactic and therapeutic treatment, we have now isolated from an expression library of B. burgdorferi (strain ZS7) three novel genes, zs7.a36, zs7.a66 and zs7.a68. All three genes are located, together with ospA/B, on the linear plasmid lp54, and are expressed in vitro and in ticks. At least temporarily two of them, ZS7.A36 and ZS7.A66, are also expressed during infection. The respective natural antigens are poorly immunogenic ininfected normal mice but elicited antibodies in Lyme disease patients. We show that recombinant preparations of ZS7.A36, ZS7.A66 and ZS7.A68 induce functional antibodies in rabbits capable of protecting immunodeficient mice against subsequent experimental infection. These findings suggest that all three recombinant antigens represent potential candidates for a "second generation" vaccine to prevent and/or cure Lyme disease.     

In vivo measurement of apparent diffusion coefficients of hyperpolarized 13C‐labeled metabolites

The combination of hyperpolarized MRS with diffusion weighting (dw) allows for determination of the apparent diffusion coefficient (ADC), which is indicative of the intra‐ or extracellular localization of the metabolite. Here, a slice‐selective pulsed‐gradient spin echo sequence was implemented to acquire a series of dw spectra from rat muscle in vivo to determine the ADCs of multiple metabolites after a single injection of hyperpolarized [1‐¹³C]pyruvate. An optimal control optimized universal‐rotation pulse was used for refocusing to minimize signal loss caused by B₁ imperfections. Non‐dw spectra were acquired interleaved with the dw spectra and these were used to correct for signal decay during the acquisition as a result of T₁ decay, pulse imperfections, flow etc. The data showed that the ADC values for [1‐¹³C]lactate (0.4–0.7 µm²/ms) and [1‐¹³C]alanine (0.4–0.9 µm²/ms) were about a factor of two lower than the ADC of [1‐¹³C]pyruvate (1.1–1.5 µm²/ms). This indicates a more restricted diffusion space for the former two metabolites consistent with lactate and alanine being intracellular. The higher ADC for pyruvate (similar to the proton ADC) reflected that the injected substance was not confined inside the muscle cells but also present extracellular. Copyright © 2014 John Wiley & Sons, Ltd.     

Social Media and Rating Sites as Tools to Understanding Quality of Care: A Scoping Review

Background

Insight into the quality of health care is important for any stakeholder including patients, professionals, and governments. In light of a patient-centered approach, it is essential to assess the quality of health care from a patient’s perspective, which is commonly done with surveys or focus groups. Unfortunately, these “traditional” methods have significant limitations that include social desirability bias, a time lag between experience and measurement, and difficulty reaching large groups of people. Information on social media could be of value to overcoming these limitations, since these new media are easy to use and are used by the majority of the population. Furthermore, an increasing number of people share health care experiences online or rate the quality of their health care provider on physician rating sites. The question is whether this information is relevant to determining or predicting the quality of health care.

Objective

The goal of our research was to systematically analyze the relation between information shared on social media and quality of care.

Methods

We performed a scoping review with the following goals: (1) to map the literature on the association between social media and quality of care, (2) to identify different mechanisms of this relationship, and (3) to determine a more detailed agenda for this relatively new research area. A recognized scoping review methodology was used. We developed a search strategy based on four themes: social media, patient experience, quality, and health care. Four online scientific databases were searched, articles were screened, and data extracted. Results related to the research question were described and categorized according to type of social media. Furthermore, national and international stakeholders were consulted throughout the study, to discuss and interpret results.

Results

Twenty-nine articles were included, of which 21 were concerned with health care rating sites. Several studies indicate a relationship between information on social media and quality of health care. However, some drawbacks exist, especially regarding the use of rating sites. For example, since rating is anonymous, rating values are not risk adjusted and therefore vulnerable to fraud. Also, ratings are often based on only a few reviews and are predominantly positive. Furthermore, people providing feedback on health care via social media are presumably not always representative for the patient population.

Conclusions

Social media and particularly rating sites are an interesting new source of information about quality of care from the patient’s perspective. This new source should be used to complement traditional methods, since measuring quality of care via social media has other, but not less serious, limitations. Future research should explore whether social media are suitable in practice for patients, health insurers, and governments to help them judge the quality performance of professionals and organizations.