Research Spotlight

Baylor Health Sciences Library brings to you each month the latest published research from the Baylor Scott & White and Texas A&M College of Dentistry communities. Each newly published article features the researcher, the abstract, and link to the full text. For information on including your own research, please contact Sudha Ramakrishnan at Sudha.Ramakrishnan@BSWHealth.org for BSWH or at sudharamakrishnan@tamu.edu for COD.


Posted January 15th 2021

Internal Medicine 2035: Preparing the Future Generation of Internists.

Christian T. Cable M.D.

Christian T. Cable M.D.

Yun, H.C., Cable, C.T., Pizzimenti, D., Desai, S.S., Muchmore, E.A., Vasilias, J., Thomas, C., Nasca, T.J. and Lieh-Lai, M.W. (2020). “Internal Medicine 2035: Preparing the Future Generation of Internists.” J Grad Med Educ 12(6): 797-800

Full text of this article.

Residency education should prepare physicians for practice. While no one would intentionally design a residency program otherwise, planning program requirements to meet this aim is difficult. Substantial changes in program requirements take years to establish. With the rapid changes in health care, program requirements that are appropriate in 2020 will be out of date by the time that the residents trained entirely under those requirements graduate. [No abstract; excerpt from article].


Posted January 15th 2021

Preferential accumulation of the active S-(+) isomer in murine retina highlights novel mechanisms of vigabatrin-associated retinal toxicity.

Teodoro Bottiglieri, Ph.D.

Teodoro Bottiglieri, Ph.D.

Walters, D.C., Jansen, E.E.W., Salomons, G.S., Arning, E., Ashcraft, P., Bottiglieri, T., Roullet, J.B. and Gibson, K.M. (2020). “Preferential accumulation of the active S-(+) isomer in murine retina highlights novel mechanisms of vigabatrin-associated retinal toxicity.” Epilepsy Res Dec 29;170:106536. [Epub ahead of print].

Full text of this article.

((S)-(+)/(R)-(-)) vigabatrin (Sabril(R); γ-vinyl GABA), an antiepileptic irreversibly inactivating GABA-transaminase, was administered to male C57Bl6 J mice via continuous infusion (0, 40, 80 mg/kg/d) for 12 days. Our study design pooled retina, eye (minus retina), whole brain and plasma from n = 24 animals for each dose to provide n = 8 triplicates per treatment group. Hypothesizing that (S)-(+) VGB (active isomer) would preferentially accumulate in retina, we determined VGB isomers, comprehensive amino acids, and pharmacokinetic parameters. In brain, eye and plasma, the ((S)-(+)/(R)-(-)) ratio varied from 0.73 to 1.29 and 13.3 in retina, accompanied by a partition coefficient (tissue/plasma, ((S)-(+);(R)-(-))) of 5.8;0.34, 0.63;0.49, and 0.51;0.34 in retina, eye and brain, respectively. Racemic VGB (nmol/g; plasma, nmol/mL, range of means for dose) content was: retina, 25-36; eye (minus retina), 4.8-8.0; brain, 3.1-6.8 and plasma, 8.7-14.9. GABA tissue content (nmol/g) was 1246-3335, 18-64 and 2615-3200 as a function of VGB dose for retina, eye (minus retina) and brain, respectively. The retinal glial cell toxin 2-aminoadipic acid also increased with VGB dose (76-96 nmol/g). Partitioning of active (S)-(+) VGB to retina suggests the involvement of a stereospecific transporter, the identification of which could reveal new therapeutic paradigms that might mitigate VGB’s well-known retinal toxicity and expand its clinical utility.


Posted January 15th 2021

Non-coding RNAs and potential therapeutic targeting in cancer.

Shusuke Toden Ph.D.

Shusuke Toden Ph.D.

Toden, S., Zumwalt, T.J. and Goel, A. (2020). “Non-coding RNAs and potential therapeutic targeting in cancer.” Biochim Biophys Acta Rev Cancer 1875(1): 188491.

Full text of this article.

Recent advances have begun to clarify the physiological and pathological roles of non-coding RNAs (ncRNAs) in various diseases, including cancer. Among these, microRNAs (miRNAs) have been the most studied and have emerged as key players that are involved in the regulation of important growth regulatory pathways in cancer pathogenesis. The ability of a single ncRNA to modulate the expression of multiple downstream gene targets and associated pathways, have provided a rationale to pursue them for therapeutic drug development in cancer. In this context, early data from pre-clinical studies have demonstrated that synthetic miRNA-based therapeutic molecules, along with various protective coating approaches, has allowed for their efficient delivery and anti-tumor activity. In fact, some of the miRNA-based cancer therapeutic strategies have shown promising results even in early-phase human clinical trials. While the enthusiasm for ncRNA-based cancer therapeutics continue to evolve, the field is still in the midst of unraveling a more precise understanding of the molecular mechanisms and specific downstream therapeutic targets of other lesser studied ncRNAs such as the long-non-coding RNAs, transfer RNAs, circular RNAs, small nucleolar RNAs, and piwi-interacting RNAs. This review article provides the current state of knowledge and the evolving principles for ncRNA-based therapeutic approaches in cancer, and specifically highlights the importance of data to date and the approaches that are being developed to overcome the challenges associated with their delivery and mitigating the off-target effects in human cancers.


Posted January 15th 2021

Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020.

Manjusha Gaglani M.D.

Manjusha Gaglani M.D.

Tenforde, M.W., Talbot, H.K., Trabue, C.H., Gaglani, M., McNeal, T.M., Monto, A.S., Martin, E.T., Zimmerman, R.K., Silveira, F., Middleton, D.B., Olson, S.M., Garten Kondor, R.J., Barnes, J.R., Ferdinands, J.M. and Patel, M.M. (2020). “Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020.” J Infect Dis Dec 30;jiaa800. [Epub ahead of print].

Full text of this article.

BACKGROUND: Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. METHODS: We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. RESULTS: 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. CONCLUSIONS: In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.


Posted January 15th 2021

Effect of antigenic drift on influenza vaccine effectiveness in the United States – 2019-2020.

Arundhati Rao, M.D.

Arundhati Rao, M.D.

Tenforde, M.W., Kondor, R.J.G., Chung, J.R., Zimmerman, R.K., Nowalk, M.P., Jackson, M.L., Jackson, L.A., Monto, A.S., Martin, E.T., Belongia, E.A., McLean, H.Q., Gaglani, M., Rao, A., Kim, S.S., Stark, T.J., Barnes, J.R., Wentworth, D., Patel, M.M. and Flannery, B. (2020). “Effect of antigenic drift on influenza vaccine effectiveness in the United States – 2019-2020.” Clin Infect Dis Dec 25;ciaa1884. [Epub ahead of print].

Full text of this article.

BACKGROUND: At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses, that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses. METHODS: We enrolled outpatients aged ≥6 months with acute respiratory illness at five sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus sub-type/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. RESULTS: Among 8,845 enrollees, 2,722 (31%) tested positive for influenza, including 1,209 (44%) for B/Victoria and 1,405 (51%) for A(H1N1)pdm09. Effectiveness against any influenza illness was 39% (95% confidence interval [CI]: 32-44), 45% (95%CI: 37-52) against B/Victoria and 30% (95%CI: 21-39) against A(H1N1)pdm09 associated illness. Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95%CI: -14 to 23%) which predominated after January. CONCLUSIONS: Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed.